Use of a 15 k gene microarray to determine gene expression changes in response to acute and chronic...

Use of a 15 k gene microarray to determine geneexpression changes in response to acute and chronicmethylmercury exposure in the fathead minnow

Pimephales promelas Rafinesque

R. KLAPER*†, B. J. CARTER‡, C. A. RICHTER§, P. E. DREVNICKk,M. B. SANDHEINRICH{ AND D. E. TILLITT§

*Great Lakes WATER Institute, University of Wisconsin–Milwaukee, 600 East GreenfieldAvenue, Milwaukee, WI 53204, U.S.A., ‡EcoArray, 12085 Research Drive, Alachua, FL

32615, U.S.A., §Columbia Environmental Research Center, USGS, 4200 New HavenRoad, Columbia, MO 65201, U.S.A., kDepartment of Marine Chemistryand Geochemistry, Woods Hole Oceanographic Institution, Woods Hole,

MA 02543, U.S.A. and {Department of Biology, University of Wisconsin-La Crosse,La Crosse, WI 54601, U.S.A.

This study describes the use of a 15 000 gene microarray developed for the toxicological model

species, Pimephales promelas, in investigating the impact of acute and chronic methylmercury

exposures in male gonad and liver tissues. The results show significant differences in the

individual genes that were differentially expressed in response to each treatment. In liver, a total

of 650 genes exhibited significantly (P < 0�05) altered expression with greater than two-fold

differences from the controls in response to acute exposure and a total of 267 genes were

differentially expressed in response to chro*nic exposure. A majority of these genes were

downregulated rather than upregulated. Fewer genes were altered in gonad than in liver at both

timepoints. A total of 212 genes were differentially expressed in response to acute exposure and

155 genes were altered in response to chronic exposure. Despite the differences in individual

genes expressed across treatments, the functional categories that altered genes were associated

with showed some similarities. Of interest in light of other studies involving the effects of

methylmercury on fish, several genes associated with apoptosis were upregulated in response to

both acute and chronic exposures. Induction of apoptosis has been associated with effects on

reproduction seen in the previous studies. This study demonstrates the utility of microarray

analysis for investigations of the physiological effects of toxicants as well as the time-course of

effects that may take place. In addition, it is the first publication to demonstrate the use of this

new 15 000 gene microarray for fish biology and toxicology. # 2008 The Authors

Journal compilation # 2008 The Fisheries Society of the British Isles

Key words: apoptosis; fathead minnow; genomics; methylmercury; microarray; toxicogenomics.

INTRODUCTION

In recent years, genomics has emerged as a powerful and sensitive tool for theinvestigation of the effect of environmental change on fishes and other aquatic

†Author to whom correspondence should be addressed. Tel.: þ1 414 382 1713; fax: þ1 414 382 1705;

email: [email protected]

Journal of Fish Biology (2008) 72, 2207–2280

doi:10.1111/j.1095-8649.2008.01899.x, available online at http://www.blackwell-synergy.com

2207# 2008 The Authors

Journal compilation # 2008 The Fisheries Society of the British Isles

organisms (Klaper & Thomas, 2004; Thomas & Klaper, 2004). By measuringexpression of thousands of genes at once, genomics provides a simultaneous mea-surement of the changes that are occurring in multiple biochemical pathways ina tissue. These techniques complement traditional environmental risk assessments.Standard studies of the consequences of exposure to a stressor often measure grossresponses in the form of mortality, changes in growth or reproductive declines anddo not aid in defining a mechanism of action. Genomic techniques aid in the eval-uation of an organismal response by providing a more detailed analysis of ef-fects and modes of action as well as a means to generalize across stressors andspecies (Klaper & Thomas, 2004; Snape et al., 2004).Methylmercury is a common environmental contaminant formed when in-

organic mercury is methylated by environmental bacteria. It is known to be aneurotoxin, and in developing mammals, it has been found to cause significantneurological problems (Zelikoff et al., 1995; National Research Council, 2000).However, the effects of methylmercury on other physiological processes, suchas reproduction, are relatively unknown.Studies of the impact of methylmercury contamination in fish in particular have

found declines in reproductive hormones, smaller gonad development or atro-phy, delays in spawning and effects on fecundity (Wester, 1991; Kirubagaran &Joy, 1992; Friedmann et al., 1996; Hammerschmidt et al., 2002; Drevnick &Sandheinrich, 2003). The mechanisms that cause these effects are unclear; how-ever, in the previous study using a 200 gene macroarray (Klaper et al., 2006),the authors found that methylmercury exposure in fathead minnows Pime-phales promelas Rafinesque induced changes in the expression of genes com-monly associated with endocrine disruption, most specifically, alterations inthe regulation of vitellogenin mRNA in female fish. The pattern of expressionof these genes as well as others indicated a difference in the mechanism ofaction between methylmercury and other endocrine disrupting compounds.Apoptosis has been suggested in the study of Klaper et al. as well as in other

studies as an alternative mechanism that may mediate these effects. In anotherpaper, Gonzalez et al. (2005) examined the effect of dietary methylmercury onthe expression of 13 genes in muscle, liver and brain tissues of zebrafish Daniorerio (Hamilton). They found an increase in the expression of genes associatedwith production of reactive oxygen species [cytochrome c oxidase subunit I,cytoplasmic superoxide dismutase (coxl, sod)] that are also associated with apo-ptosis. These specific genes were not differentially expressed in the fatheadstudy. However, genes associated with apoptosis were altered in the study byKlaper et al.. The differences in the genes identified by Gonzalez et al. andKlaper et al. may be partly attributed to the dose provided to the fishes becauseGonzalez et al. provided a much larger dose, higher than the levels documentedin wild populations of fishes. Species differences and duration of exposure mayalso contribute to the differences between these studies. Other studies havedocumented apoptosis in reproductive tissues with methylmercury exposurein fish and rats at environmentally relevant levels (Homma-Takeda et al.,2001; Drevnick et al., 2006). The liver is critically linked to reproductive hor-mones (testosterone and oestrogen metabolism as well as vitellogenin production)in fish species, and therefore, liver apoptosis may be related to reproductivedysfunction. Apoptosis is a recognized part of follicular development and

2208 R. KLAPER E T A L .

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Journal compilation # 2008 The Fisheries Society of the British Isles, Journal of Fish Biology 2008, 72, 2207–2280

reproductive function in the gonad; however, abnormal increases in apoptoticevents may have a significant effect on fecundity or could reduce the ability ofa tissue to respond to hormone signals.Since the time of the previous fathead minnow study, a new microarray has

been developed for the fathead minnow that incorporates sequences from over250 000 expressed sequence tags (ESTs) sequenced by the Department ofEnergy Joint Genome Institute (JGI) in co-operation with the EnvironmentalProtection Agency (EPA: Larkin et al., 2007). The study presented here com-pares the changes in gene expression in liver and gonad of male fathead min-nows after methylmercury exposure that mimics exposures documented tocommonly occur in wild fish populations (Hammerschmidt et al., 2002). Thisstudy also compares these changes over two time frames, a 4 day acute expo-sure and a chronic 600 day methylmercury exposure. It expands on the previ-ous microarray study (Klaper et al., 2006) by using this larger microarray (15000 genes v. 200 genes) from EcoArray (Gainesville, FL, U.S.A.). The goal ofthis research was to examine the short-term and long-term changes in geneexpression that occur after toxicant exposure and to identify the physiologicalmechanisms that may cause the changes in reproduction and endocrine func-tion seen in other experiments.

MATERIALS AND METHODS

MICROARRAYS

The 15 k feature microarray used for this study is the third generation of high-density oligonucleotide microarrays developed by EcoArray (Alachua, FL, U.S.A.) forbroad use in ecotoxicogenomics research with the fathead minnow, a species with a longhistory of use in aquatic toxicology research (Ankley et al., 2006). Prior to the develop-ment of the oligonucleotide arrays, very few fathead minnow cDNA sequences or ESTswere publicly available or available in an array format. To obtain more gene sequences,EcoArray developed a variety of fathead minnow cDNA and suppression subtractivehybridization libraries from multiple tissues, including gonad, liver, brain, heart andspleen from both male and female fathead minnows (Larkin et al., 2007). Concurrentwith EcoArray’s intensive sequencing effort, the JGI sequenced 250 000 cDNA clonesfrom fathead minnows and made the ESTs publicly available in August 2005 [NationalCenter for Biotechnology Information (NCBI) nucleotide database]. Clustering of thesecombined EST sequences and addition of more recent cDNA sequences submitted toGenBank (NCBI) yielded over 15 k unique fathead minnow genes, which were used todevelop a second generation 15 k gene oligonucleotide microarray.

Probes for each gene were designed using Agilent software (Agilent Technologies,Palo Alto, CA, U.S.A.) and 60-mer oligonucleotides were synthesized in situ on treatedglass slides using inkjet deposition technology (Larkin et al., 2007). Each unique probewas annotated with the gene name derived from the highest confidence match of the six-frame translation against the non-redundant (nr) protein database (NCBI). If the nr searchfailed to yield a match with e-value < 0�001, then the gene name was based on a searchof the nucleotide (nt) database (NCBI). Annotation also included biological process,cellular component and molecular function gene ontology (GO) terms (where avail-able), the top basic local alignment search tool (BLAST) hit from the nr database alongwith accession number and e-value; and the top BLAST hit from the nt database alongwith its accession number and e-value. In cases in which the direction of a gene couldnot be determined, probes were synthesized from both the strands (forward and reversecomplement) (Larkin et al., 2007). Control spots for internal quality assurance–quality

ACUTE AND CHRONIC RESPONSES TO METHYLMERCURY 2209

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control (QA–QC) metrics were also added (proprietary Agilent control spots standardon Agilent arrays).

Because of advances in inkjet printing, high-density microarrays are now beingprinted at a greatly reduced cost. The fathead minnow microarray is now in its thirdgeneration and has been available for academic and commercial use since March2007 in two formats. The 4 � 44 k format (4 microarrays per glass slide) containsthe same 22 k 60-mer oligonucleotides discussed above, but they are printed in dupli-cate, increasing the reliability of analysis. This microarray is almost fully annotatedwith over 80% of the genes matched to named genes found in publicly available data-bases (www.ecoarray.com). The unnamed oligonucleotides make it possible to discover‘new’ genes. The second format (8 � 15 k) contains eight arrays per slide and has over15 200 genes. These genes are a sub-set of the 22 k genes and are 100% annotated. All‘no hit’ genes and any duplicates (by accession number) were removed, leaving only thebest named genes on this microarray. This array was used for this experiment and iscurrently being used to test 14 different chemical compounds for other experiments(B. Carter, pers. comm.). The probe sequences for each of the genes are available(under licence agreement) from EcoArray. GO information, when available, is providedfor both array formats. Array annotation is updated regularly.

FATHEAD MINNOW ACUTE EXPOSURES

Standard conditions were used to conduct 96 h exposures of fathead minnows. Male(2�3 � 0�6 g fish�1) adult fish were exposed. Water quality was monitored daily for oxy-gen (7�1 mg l�1, range 6�7–7�7 mg l�1), pH (mean 8�3, range 8�3–8�7), hardness (mean284 mg CaCO3 l�1, range 280–288 mg CaCO3 l�1), alkalinity (mean 243 mg l�1, range240–256 mg l�1) and total ammonia (mean 0�06 mg l�1, range 0�04–0�10 mg l�1). Waterturnover in the tanks was at a rate of 2�5 times day�1 and temperature was 21�4 � 0�4°C. In order to control the internal concentration, methylmercury (Sigma-Aldrich,St Louis, MO, U.S.A.; catalogue number 442534-5G-A) was delivered in a single intraper-itoneal injection (in a 0�02 M Na2CO3 solution). Treated fish were given an injection ofa sublethal concentration of methylmercury, 2�0 mg g�1 body mass, and controls weregiven a vehicle injection without methylmercury. The experiment consisted of 12 repli-cate male fish injected for each treatment group. Fish were housed six per tank, segre-gated by treatment. There was no mortality during treatment. At the end of thetreatment period, fish were euthanized with an overdose of MS-222 and livers and go-nads were removed and quick frozen in liquid nitrogen.

FATHEAD MINNOW CHRONIC EXPOSURES

Fathead larvae were raised until they were large enough to feed on diet (90 dayspost-hatch) and 200 minnows (mixed male and female) were transferred to each of fif-teen 180 l flow-through aquaria for exposure studies. Aquaria were filled with wellwater, temperature was maintained at 23�6 � 0�1° C and each received a 16 h light:8 hdark photoperiod cycle. Fathead minnows were maintained in aquaria receiving wellwater with a 16 h light:8 h dark cycle. Water quality characteristics were measureddaily (dissolved oxygen 6�70 � 0�01 mg l�1) or weekly (alkalinity 300 � 2 mg l�1 asCaCO3, pH 8�06 � 0�01, hardness 348 � 3 mg l�1 as CaCO3, ammonia 0�2 � 0�0mg l�1 as NH3-N). Deposited and suspended wastes were siphoned daily from eachaquarium, and residue on aquaria was removed weekly by scraping. Minnows werefed either control levels of methylmercury (0�058 � 0�004 mg g�1) or a higher methyl-mercury treatment (3�93 � 0�08 mg g�1) by dry mass. This higher concentration was de-signed to be representative of the diets of insectivorous and piscivorous fish from somemidcontinental low alkalinity lakes contaminated with Hg from non-point sources(Hammerschmidt et al., 2002). Diets were prepared by mixing food with methylmercu-ric chloride in alcohol. Control diets were mixed with alcohol alone. Alcohol was evap-orated from the food and the diet was frozen until use. Fish were fed 5% of their body


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mass of their respective food treatment for 600 days, corresponding to the end of a com-plementary behaviour experiment. There was no difference in mortality or growth of fishin control v. treated tanks. After 600 days, the fish were euthanized. The liver and gonadwere harvested, placed in Trizol reagent (Invitrogen, Carlsbad, CA, U.S.A.) and kept at�80° C until extraction. RNA was extracted according to Trizol protocol.

MICROARRAY GENE EXPRESSION

For this experiment, male fathead minnows were chosen for comparison amongtreatments. Microarray hybridizations were conducted at EcoArray Inc. Total RNAfor the short-term (96 h) samples was processed using RNEasy Plus spin columns(Qiagen Inc., Valencia, CA, U.S.A.), which includes a DNase treatment step. Forthe 300 day exposures, total RNA was extracted from each of the tissue homogenates(liver and gonad), DNase-treated (DNA free) RNA was extracted for five or moresamples of each tissue, and the integrity of all RNA samples was examined using aBioAnalyzer 2100 (Agilent Technologies Inc., Santa Clara, CA, U.S.A.). Four sam-ples were selected with 260–280 and 260–230 ratios closest to 2�0. We used a one-colour design for this project, following the protocol established by Agilent Technol-ogies (version 5.5 of February 2007). For each experimental sample, the cyanine-3(cy-3) fluorescent label was incorporated directly into the cRNA during the in vitrotranscription labelling reaction using Agilent’s Low RNA Input Linear Amplificationkit. This method uses T7 RNA polymerase, which simultaneously amplifies the targetmaterial and incorporates the cy-3 label. For each protocol, 7 ml of Agilent controlspikes were added to each 900 ng sample (Agilent’s RNA Spike-In Kit, One Color)to hybridize to control spots on the arrays for quality control and dynamic range.The resultant cRNA was purified using a modified protocol for Qiagen’s RNeasymini-spin columns and then analysed for dye incorporation rates and quantity ona NanoDrop ND-1000 spectrophotometer. Equal quantities (600 ng) of the cy-3labelled samples were fragmented prior to hybridization, mixed with 2� GE Hybrid-ization Buffer HI-RPM (GE Healthcare, Chalfont St Giles, U.K.) and then applied tothe microarray. Slides were hybridized in a stainless steel hybridization chamber that‘sandwiches’ the hybridization buffer and samples between the microarray slide anda gasket slide, creating a leak-proof chamber. They were hybridized at 65° C for 17h in a rotor oven. Images were acquired from the hybridized gene chips using an Agi-lent scanner. Four biological replicates were run for each tissue (liver and gonad) forcontrols and treated fish and for each time period for a total of 32 microarrays.

DATA ANALYSIS

Data from the arrays were extracted using Feature Extraction 9.0 (Agilent Techno-logies). The .txt files were imported into GeneSpring (GS: Agilent Technologies) andpreprocessed using the ‘Enhanced Agilent FE Import’ macro. GeneSpring convertedthe Feature Extraction software flags (e.g. population and non-uniformity outliers) intothe GS flags (present, marginal, absent or unknown) and compared signal intensity withthe localized background. All genes were normalized according to the GS preset pro-tocol for one-colour microarrays (data measurements <0�01 to 0�01; per chip normal-izes to 50th percentile; per spot: normalizes to median). Genes were filtered on flagsand only those genes that were marked ‘present’ in at least four of the 32 arrays wereincluded in subsequent analyses (n ¼ 12 671). This removes all features that are veryclose to background or mislabelled and leads to more reliable statistical results. One-way ANOVA was selected to compare treatments with their respective controls.

Statistical analysis of GO (Ashburner et al., 2000) terms was conducted with the fastassignment and transference of information (FatiGO) web tool (Al-Shahrour et al.,2005, 2006). This tool uses Fisher’s exact test to detect differences in frequency ofGO terms associated with two lists of genes. P-values were not adjusted for multiplecomparisons because the available methods for multiple comparison testing are too


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conservative for the purpose, the discovery of gene classes associated with response tomethylmercury exposure. FatiGO analysis was used to determine the differentialdistributions of Biological Process GO terms between genes that were altered andunaltered in response to each treatment to determine which categories were statisticallyoverrepresented v. their presence on the array.

QUANTITATIVE POLYMERASE CHAIN REACTION OFRELEVANT GENES

Individual genes were chosen for quantitative polymerase chain reaction (qPCR)based on available primers and significance to the results from the array experiment. Eachprimer set was validated for specificity and efficiency by running dissociation and stan-dard curves, respectively. A melting (dissociation) curve was generated to check for pres-ence of non-specific PCR products (data not shown). Standard curves included data froma minimum of five serially diluted cDNA samples (50, 5, 0�5, 0�05 and 0�005 ng).

For each sample, 1 mg of DNase-treated (DNA-free; Ambion Inc., Austin, TX, U.S.A.)total RNA from mercury exposed and control tissue was reverse transcribed to single-strand cDNA according to the manufacturer’s instructions using the High-CapacitycDNA Archive Kit (Applied Biosystems, Foster City, CA, U.S.A.). This kit contains ran-dom primers and Multiscribe reverse transcriptase (RT). An Eppendorf MasterCyclerGradient Thermocycler (Eppendorf, Hamburg, Germany) was programmed with a singlecycle as follows: 25° C for 10 min, 37° C for 120 min (2 h) and 4° C to end the cycle andhold. cDNA was stored at �20° C if not used immediately.

Real-time PCR was performed in 25 ml reactions that contained 100 ng cDNA for allprimers, 12�5 ml SYBR Green Master Mix (Applied Biosystems, P/N 4309155) whichincluded SYBR Green, buffer, Taq polymerase, deoxynucleotide triphosphates (dNTP)and 50 nM each of the forward and reverse primers. For all the samples, minus RTcontrols were also run to ensure the removal of all contaminating DNA. An AppliedBiosystems 7500 thermocycler was used for the PCR reactions with the following cyclevariables: 1 cycle of 50° C for 2 min, 1 cycle of 95° C for 10 min and 40 cycles of 95° Cfor 15 s and 60° C for 60 s.

Each sample was run in triplicate and the averaged value was normalized to measuredL8 rRNA values for each sample. To evaluate the results, a DDCt method of analysis wasused to compare changes in gene expression between controls and treated samples.

Primers were chosen to amplify c. 150 bp of each target gene and designed to haveapproximately similar melting temperatures (52–58° C) and a guanine and cytosine con-tent of 40–60% with minimal repeats (Table I). All primers were synthesized andhigh pressure liquid chromatography (HPLC) purified (MWG Biotech Inc., High Point,NC, U.S.A.).

RESULTS

In liver, a total of 650 genes exhibited significantly altered expression withgreater than two-fold differences from the controls (ANOVA, P < 0�05) in

TABLE I. Primers for quantitative polymerase chain reaction

Primers Name sequence

Vtg1 forward TGCTCTTCCACCTGTTTTTGCVtg1 reverse CCCAGCAGCTTGTGGTCAAHSP70 forward TGGGCTCAATGTCCTCAGAATHSP70 reverse CTGCTCCTTTGCCTTTGTCAARibL8 forward CATACCACAAGTACAAGGCCAAGARibL8 reverse ACCGAAGGGATGCTCAACAG


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response to acute exposure. Of these, 245 genes were upregulated and 405 geneswere downregulated [Fig. 1(a)]. A total of 267 genes were differentially ex-pressed (greater than two-fold change up or down, ANOVA, P < 0�05) inresponse to chronic exposure in liver. Of these, 98 were upregulated and 169genes were downregulated [Fig. 1(a)]. In gonad, fewer genes were altered thanin liver. A total of 212 genes were altered more than two-fold from the controlin response to acute exposure. Of these, 75 gonad genes were upregulated and137 genes were downregulated [Fig. 1(b)]. In response to chronic exposure, 155gonad genes were differentially expressed with a majority being downregulated

FIG. 1. Venn diagrams of genes altered in (a) liver and (b) gonad in response to methylmercury from

a total number of 15 207 probes on the array.


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(128) and 27 upregulated [Fig. 1(b)]. A full list of genes that were upregulatedor downregulated with exposures is shown in Appendix I.

GENE EXPRESSION CHANGES IN LIVER

In liver, many genes involved in protein synthesis were downregulated inresponse to acute methylmercury exposure. In particular, GO categories of bio-synthesis, tRNA processing, ribosome biogenesis, protein folding and proteintransport were significantly overrepresented among altered genes (AppendixII). We selected categories and individual genes for further attention basedon significantly overrepresented GO categories and on previous findings thatmethylmercury exposure may have effects on oxidative stress, immune func-tion, reproduction and apoptosis [Fig. 2(a) and Table II]. Most of the genesin these categories were downregulated [Fig. 2(a)]. In contrast, exogenous anti-gen presentation genes tended to be upregulated in methylmercury-exposedfish. Of the three exogenous antigen presentation genes on the microarray,two were significantly upregulated [Fig. 2(a)].In response to chronic exposure, significantly overrepresented categories

included protein targeting, induction of apoptosis, regulation of transcription,protein processing and immune response to viruses (Appendix II). Apoptosis

FIG. 2. Numbers of upregulated and downregulated genes in select gene ontology categories among genes

altered in liver in response to (a) acute and (b) chronic methylmercury exposure. Dark bars represent

genes that are upregulated and those in grey with a hatch represent genes that are downregulated.


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TABLEII.Selectedsignificantlyaltered

genes

andassociatedfunctionsin

liver

inresponse

to4daymethylm

ercury

exposure

Geneontologyfunction

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Protein

folding

EA_Pp_70638a

Protein

disulphideisomerase

familyA,mem

ber

5�1� 01

0� 023

EA_Pp_58567a

Peptidylprolylisomerase-like1

�1� 63

0� 039

EA_Pp_54884a

Heatshock

60kDaprotein

1�2� 62

0� 037

EA_Pp_57434a

Heatshock

70kDaprotein

5�3� 38

0� 028

Protein

transport

EA_Pp_55055a

Rashomologuegenefamily,mem

ber

F1� 81

0� 026

EA_Pp_60632a

RAN-bindingprotein

5�1� 06

0� 006

EA_Pp_56920a

Importin

4�1� 82

0� 036

Fattyacid

biosynthesis

EA_Pp_63086a

Acetyl-coenzyme-A

carboxylase

beta

1� 42

0� 046

EA_Pp_63832a

Stearoyl-CoA

desaturase

�1� 54

0� 047

EA_Pp_55202a

Thioesterase

domain-containing1

�1� 94

0� 028

EA_Pp_65766a

Fattyacidsynthase

�3� 10

0� 023

tRNA

processing

EA_Pp_64819a

tRNA

splicingendonuclease

2homologue

�1� 12

0� 039

EA_Pp_61433a

TruBpseudouridinesynthase

homologue1

�1� 13

0� 045

EA_Pp_67536a

tRNA

isopentenyltran

sferase1

�1� 34

0� 016

Immunefunction,

antigen

presentation

EA_Pp_68878a

Sim

ilarto

leucocyte

immune-typereceptor3

2� 59

0� 020

EA_Pp_52048a

Sim

ilarto

majorhistocompatibilitycomplex

class

IIbetachain

1� 20

0� 036

EA_Pp_69578a

Sim

ilarto

tumournecrosisfactorligand

superfamily,mem

ber

14

1� 01

0� 044

Apoptosis

EA_Pp_52527a

Mast

cellprotease

42� 34

0� 031

EA_Pp_50897a

Growth

arrest-specific2

5� 77

0� 012

EA_Pp_56718a

Caspase

3,apoptosis-relatedcysteineprotease

1� 64

0� 024


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TABLEIII.

Selectedsignificantlyaltered

genes

amonggenes

altered

inliver

inresponse

tochronic

methylm

ercury

exposure


ProbeID

GeneTitle

Logtw

o-fold

change

P-value

Carbohydrate

metabolism

EA_Pp_63866a

Galactosidase,alpha

1� 38

0� 003

EA_Pp_55682a

Xylulokinase

homologue

�1� 49

0� 014

EA_Pp_69710a

Phosphomannomutase

13� 07

0� 009

EA_Pp_58872a

Transaldolase

1�1� 28

0� 024

Electrontransport

EA_Pp_55283a

Hypotheticalprotein

FLJ23322

1� 90

0� 014

EA_Pp_52099a

NADPH-dependentdiflavin

oxidoreductase

11� 00

0� 006

EA_Pp_66495a

Protein

disulphideisomerase

familyA,mem

ber

3�1� 14

0� 037

EA_Pp_55626a

Sim

ilarto

coiled-coildomain-containing14

1� 09

0� 029

EA_Pp_56674a

Aldehydeoxidase

1�1� 20

0� 017

Regulationof

transcription

EA_Pp_67898a

Sim

ilarto

zincfinger

protein

551

1� 36

0� 026

EA_Pp_67717a

PHD

finger

protein

21A

1� 49

0� 025

EA_Pp_55262a

Polymerase

IIpolypeptideJ,

13� 3

kDa

�1� 33

0� 039

EA_Pp_54205a

Heatshock

factor2

1� 43

0� 003

EA_Pp_60472a

Tumourprotein

p53-bindingprotein

1�1� 26

0� 004

EA_Pp_62563a

SRY-box-containinggene11

�1� 38

0� 033

EA_Pp_58869a

Actin-dependentregulatorofchromatin

�1� 71

0� 039

EA_Pp_65193a

AnkyrinrepeatandBTBdomain-containing1

1� 53

0� 004

EA_Pp_58888a

Bagpipehomeoboxgene1homologue

�2� 30

0� 046

EA_Pp_66730a

BRF1homologue,

subunitofRNA

polymerase

IIItranscriptioninitiationfactorIIIB

�1� 61

0� 014

Apoptosis

EA_Pp_68560a

Microtubule-associatedprotein

tau

�1� 07

0� 024

EA_Pp_54924a

Protein

phosphatase

1,regulatory

subunit15A

1� 14

0� 027

EA_Pp_51933a

Caspase

61� 78

0� 030

EA_Pp_56718a

Caspase


1� 16

0� 020

EA_Pp_67060a

Tax1-bindingprotein

1–anti-apoptosis

1� 86

0� 017

EA_Pp_64482a

Death

effectordomain-containing1–regulation

apoptosis

2� 02

0� 044


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TABLEIII.

Continued


ProbeID

GeneTitle

Logtw

o-fold

change

P-value

Immuneresponse

EA_Pp_60220a

Majorhistocompatibilitycomplexclass

IUBA

gene

�7� 21

0� 046

EA_Pp_53694a

Sim

ilarto

tumournecrosisfactorligand

superfamilymem

ber

12

�1� 52

0� 046

Protein

folding

EA_Pp_56738a

DnaJhomologue,

subfamilyB,mem

ber

61� 11

0� 004

EA_Pp_51662a

Hypotheticalprotein

FLJ35630

2� 11

0� 041

Protein

transport

EA_Pp_50235a

Ribosome-bindingprotein

1homologue

�1� 66

0� 02

EA_Pp_52456a

Translocase

ofinner

mitochondrialmem

brane23

homologue

�1� 17

0� 047

EA_Pp_53639a


1homologue180kDa

�1� 18

0� 028

EA_Pp_55675a

Lysosomaltraffickingregulator

1� 63

0� 026

EA_Pp_55055a

MGC80698Protein

�1� 19

0� 040

EA_Pp_58919a

RAB40B,mem

ber

RASoncogenefamily

1� 61

0� 013

EA_Pp_61320a

Exocyst

complexcomponent5

1� 30

0� 012


# 2008 The Authors


and protein folding-related genes appear to be largely upregulated and immuneresponse genes were downregulated with exposure [Fig. 2(b) and Table III).

GENE EXPRESSION CHANGES IN GONAD

The GO categories significantly over represented in genes altered in thegonad in response to acute exposure are diverse and include several metabolismcategories (Appendix II). Antigen presentation was over represented, and thetwo major histocompatibility complex (MHC) genes altered in this categorywere both very strongly regulated in opposite directions [Fig. 3(a) and TableIV]. Notably, the steroid biosynthesis GO category was significantly over rep-resented among altered genes, and steroidogenic acute regulatory factor, whichis rate limiting in steroid synthesis (Stocco et al., 2005), was strongly down-regulated in testis of exposed fish (Table IV).Among genes altered in the gonad in response to chronic exposure, GO cat-

egories involved in development, the immune system and cell adhesion were sig-nificantly overrepresented (Appendix II). In the gonad, most genes within thesecategories were significantly downregulated with exposure [Fig. 3(b) and Table V].

COMPARISONS BETWEEN TREATMENTS

Overall, there appear to be a greater number of genes differentially expressedin response to the short-term exposures v. chronic methylmercury exposures.Both treatments had a larger number of downregulated genes than upregulated(Fig. 1). When genes were grouped by GO classification, there appeared to besimilarities across treatments in liver in particular (Tables II and III). Severalgenes associated with apoptosis were upregulated in response to both acuteand chronic exposures. In addition, genes associated with immune responseand protein folding appeared to be oppositely regulated, with those alteredin response to the acute exposure upregulated and those altered in responseto the chronic exposure significantly downregulated and the opposite occurringin protein folding genes. Several genes associated with protein transport weredifferentially expressed in response to both treatments: some were upregulatedand some downregulated. In gonad, similarities in GO category were restrictedto immune response and included both upregulated and downregulated genes[Fig. 2(a), (b) and Tables IV and V].Genes significantly altered within a GO category are not consistent across

treatments. There were very few individual gene changes that were similaracross treatments (Fig. 1 and Table VI). Only 12 genes were consistently down-regulated in response to both chronic and acute exposures in liver and only sixwere consistently upregulated (Table VI). The MHC class I UBA gene wasvery strongly downregulated in liver in response to both acute and chronicmethylmercury treatments (Table VI). Its variation among individuals wasgreater in the chronic treatment experiment. In gonad, there was a single gene,similar to embigin homologue, which was consistently downregulated in responseto the two treatments and none that were consistently upregulated (Table VI).The qPCR analysis of two genes, vitellogenin and hsp70, was in agreement

with the results of the microarray analysis. Vitellogenin expression in liver


# 2008 The Authors


TABLEIV

.Selectedsignificantlyaltered

genes


gonadin

response

to4daymethylm

ercury

exposure


ProbeID

Genetitle

Logtw

o-fold

change

P-value

Transcriptionfrom

RNA

polymerase

IIEA_Pp_57174a

Ets

variantgene7

1� 89

0� 030

EA_Pp_65055a

V-ets

erythroblastosisvirusE26oncogenehomologue2

1� 27

0� 005

EA_Pp_55262a

Polymerase

IIpolypeptideJ,

13� 3

kDa

�1� 23

0� 024

Rhythmic

process

EA_Pp_59608a

Hepaticleukaem

iafactor

1� 79

0� 044

EA_Pp_59573a

CCR4carboncatabolite

repression4-like

�2� 16

0� 014

Sterolbiosynthesis

EA_Pp_50801a

Isopentenyl-diphosphate

delta

isomerase

1�1� 33

0� 036

EA_Pp_58910a

Sim

ilarto

probable

ergosterolbiosynthetic

protein

28

�1� 54

0� 030

Antigen

presentation

EA_Pp_52403a

MHC

class

IUFA

gene

7� 01

0� 018

EA_Pp_60220a

MHC

class

IUBA

gene

�9� 64

0� 001

Aminoacidmetabolism

EA_Pp_64712a

Solute

carrierfamily7,mem

ber

62� 27

0� 038

EA_Pp_66130a

Cystathioninebeta-synthase

�1� 15

0� 012

EA_Pp_57186a

Glutamate

oxaloacetate

transaminase

1,soluble

�1� 19

0� 022

Steroid

biosynthesis

EA_Pp_50801a


delta

isomerase

1�1� 33

0� 036

EA_Pp_69200a

Steroidogenic

acute

regulatory

protein

�3� 06

0� 030

MHC,majorhistocompatibilitycomplex.


# 2008 The Authors


was not significantly altered in response to either acute or chronic exposure,consistent with microarray results. However, in the chronic exposure group,expression of vitellogenin was extremely variable. One of four males in thechronic exposure control group and two of four males in the chronic exposuremethylmercury-treated group had vitellogenin expression levels c. 1000-foldgreater than the average of the other samples. This is consistent with the cur-rent array data as well as previous results (Klaper et al., 2006). In the acuteexposure groups, males expressing high levels of vitellogenin were notobserved. Expression of hsp70 in liver was not altered in acute or chronic expo-sure group, consistent with microarray data.

DISCUSSION

This study indicates that methylmercury exposures cause molecular changesin liver and gonad that differ with duration of exposure. The downregulationof many genes involved in protein processing in the liver in response to acutemercury exposure suggests a general stress response. In contrast, after chronicexposure, protein folding genes were upregulated and altered protein transportgenes included both upregulated and downregulated genes, suggesting adaptation

FIG. 3. Numbers of upregulated and downregulated genes in select gene ontology categories among genes

altered in gonad in response to (a) acute 4 day methylmercury exposure or (b) chronic

methylmercury exposure. Dark bars represent genes that are upregulated and those in grey with

a hatch represent genes that are downregulated.


# 2008 The Authors


TABLEV.Selectedsignificantlyaltered

genes


gonadin

response

tochronic

methylm

ercury

exposure


ProbeID

Genename

Logtw

o-fold

change

P-value

Transcription

EA_Pp_53536a

Sim

ilarto

zonadhesin

�2� 98

0� 0022

EA_Pp_60742a

Zincfinger

protein

286

�1� 42

0� 0156

EA_Pp_51089a

Transcriptionfactor4

�1� 04

0� 0081

Inductionofapoptosis

EA_Pp_56320a

Complementcomponent7

1� 39

0� 0403

Celladhesion

EA_Pp_55605a

Scavenger

receptorclass

B,mem

ber

1�1� 46

0� 0268

EA_Pp_57879a

Protein

FLRT2precursor

�1� 53

0� 0442

EA_Pp_70488a

Bystin-like

�1� 31

0� 0166

EA_Pp_58978a

Sim

ilarto

vascularcelladhesion

protein

1�1� 00

0� 0313

EA_Pp_62849a

Precursor

�2� 44

0� 0022

EA_Pp_51160a

Neuroligin

1�2� 06

0� 0039

G-protein-coupledreceptor

protein

signallingpathway

EA_Pp_70355a

G-Protein-coupledreceptor35

�1� 33

0� 0426

EA_Pp_62330a

Cysteinylleukotrienereceptor2

�1� 23

0� 0110

Gametogenesis;meiosis

EA_Pp_57419a

Hypotheticalprotein

FLJ22349

�2� 32

0� 0119

Immunerelated

Positivethymic

T-cellselection

T-cellproliferation

EA_Pp_51389a

Dedicatorofcytokinesis2

2� 31

0� 0145

Innate

immuneresponse

EA_Pp_55507a

Properdin

Pfactor,complement

�1� 01

0� 0264

Cell–cellsignalling;inflammatory

response

EA_Pp_57136a

Sim

ilarto

CXC

chem

okine

�1� 26

0� 0282

Regulationoftranscription

EA_Pp_70706a

Neurogenic

differentiation1

�1� 12

0� 0226

EA_Pp_68031a

Ventralanteriorhomeobox1

�1� 80

0� 0083


# 2008 The Authors


TABLEVI.

Genes

altered

inboth

acute

andchronic

methylm

ercury

exposures


ProbeID

Genename

Acute

log

two-fold

change

Acute

P-value

Chronic

log

two-fold

change

Chronic

P-value

Gonad,downregulatedin

both

acute

andchronic

exposures

Celladhesion

EA_Pp_57046a

Sim

ilarto

embigin

homologue

�2� 25

0� 024

�1� 40

0� 028

Liver,upregulatedin

both

acute

andchronic

exposures

Protein

folding

EA_Pp_51662a

Hypotheticalprotein

FLJ35630

1� 81

0� 034

2� 11

0� 042

Celldeath

EA_Pp_62192a

CG33248-PA

1� 66

0� 017

1� 70

0� 030

Proteolysis

EA_Pp_56718a

Caspase

3,apoptosis-related

cysteineprotease

1� 64

0� 024

1� 16

0� 020

Protein

transport

EA_Pp_58919a

RAB40B,mem

ber

RASoncogene

family

1� 51

0� 046

1� 62

0� 013

Signaltransduction

EA_Pp_56149a

Periodhomologue4

1� 14

0� 023

2� 16

0� 013

EA_Pp_50910a

Sim

ilarto

MGC81165protein

1� 02

0� 037

2� 20

0� 019

Liver,downregulatedin

both

acute

andchronic

exposures

Protein

transport

EA_Pp_50235a


1homologue

�1� 07

0� 045

�1� 66

0� 020

EA_Pp_50256a

WD

repeatdomain

75

�1� 13

0� 009

�1� 07

0� 048

EA_Pp_63395a

Hypotheticalprotein

FLJ13089

�1� 20

0� 023

�1� 08

0� 027

Transport

EA_Pp_52843a

Cryptochrome2b

�1� 58

0� 001

�1� 65

0� 014

Transport

EA_Pp_57472a

Sim

ilarto

protein

KIA

A0133

�1� 63

0� 034

�1� 37

0� 042

Electrontransport

EA_Pp_66495a

Protein

disulphideisomerase

family

A,mem

ber

3�1� 74

0� 044

�1� 14

0� 037

Positiveregulationof

transcription

EA_Pp_66730a

BRF1homologue,

subunitofRNA

polymerase

IIItranscription

initiationfactorIIIB

�1� 79

0� 006

�1� 61

0� 015

EA_Pp_59334a

Nucleolarprotein

5�1� 86

0� 031

�1� 14

0� 035


# 2008 The Authors


TABLEVI.

Continued


ProbeID

Genename

Acute

log

two-fold

change

Acute

P-value

Chronic

log

two-fold

change

Chronic

P-value

Protein

amino

acidN-linked

glycosylationthrough

asparagine

EA_Pp_69363a

Dolichyl-di-phosphooligosaccharide-

protein

glycotransferase

�1� 99

0� 050

�1� 66

0� 028

EA_Pp_53999a

Angio-associatedmigratory

cellprotein

�2� 10

0� 037

�1� 28

0� 048

EA_Pp_52975a

Sim

ilarto

DEAH

box

polypeptide30isoform

2�3� 44

0� 032

�1� 84

0� 011

Antigen

presentation

EA_Pp_60220a

Majorhistocompatibilitycomplex

class

IUBA

gene

�9� 40

0� 000

�7� 21

0� 046

Liver,upregulatedin

acute

exposure

butdownregulatedin

chronic

exposure

Electrontransport

EA_Pp_56674a

Aldehydeoxidase

13� 65

0� 032

�1� 20

0� 017

Protein

transport

EA_Pp_55055a

Rashomologuegenefamily

1� 81

0� 026

�1� 19

0� 040

Imprinting

EA_Pp_59567a

DNA

methyltransferase

3B

1� 47

0� 033

�1� 69

0� 027

Endocytosis

EA_Pp_60698a

Dynamin

21� 20

0� 040

�1� 20

0� 007


# 2008 The Authors


to the mercury-induced stressor. Differences seen between the two exposuretypes could be because of the accumulation of methylmercury in tissues overtime that could lead to an overall increase in methylmercury exposure withtime. Studies have shown that methylmercury excretion rates in fish are veryslow, possibly exceeding the 600 days of the chronic experiment (Trudel & Ras-mussen, 1997). Fish that were harvested in the chronic experiment after 250days had levels of methylmercury that were at or exceeding the oral dose(3�93 mg g�1) of methylmercury (Drevnick & Sandheinrich, 2003) and severalfishes from the longer study that were analysed at the end of the experimentcontained levels of methylmercury that were up to 30 mg g�1 dry mass. Thereis a much smaller chance that the method of delivery (injection in the acuteand oral in the chronic) caused these differences.Oxidative stress, binding to sulfhydryl groups of cellular proteins and dis-

placement of essential metals from metallothionein are well-established mecha-nisms of mercury toxicity that could produce stress in exposed fish (Lyneset al., 2006). Other studies on gene expression related to methylmercury expo-sure have found differential expression of genes associated with oxidativestress. Gonzalez et al. (2005) found changes in the expression of glutathioneS transferase (GST) and superoxide dismutase (SOD) with exposures to meth-ylmercury. However, as noted previously, Gonzalez et al. (2005) treated theirzebrafish at doses that were much higher than the concentrations of methyl-mercury used in the current study. In the previous study, the authors didnot find that these genes were altered with methylmercury exposure (Klaperet al., 2006), and this was also the case for both the treatments in this study,indicating a potential for species differences or for a different mechanismaffecting tissues at lower methylmercury levels.In the study, several of the altered genes point to methylmercury-induced

apoptosis after both acute and chronic exposures either directly or throughassociated pathways. Methylmercury has been shown to cause apoptosis inboth cell culture experiments and whole organism experiments (Drevnicket al., 2006; Usuki et al., 2007). Most closely related to this study, methylmer-cury significantly increased the number of apoptotic follicular cells in ovarianfollicles of fathead minnows exposed to chronic oral doses of methylmercury(Drevnick et al., 2006). This led to a decline in the production of sex steroidsas well as a significant drop in fecundity.The author’s array data indicate differential expression of genes involved in

apoptosis associated, including cell adhesion, phospholipid biosynthesis, sugarmetabolism, interference with gonadotropin pathways, calcium regulation,phospholipid biosynthesis and plasma transport of proteins. A decline in fattyacid synthase mRNA expression was seen in liver in response to the acute ex-posures, and inhibition of fatty acid synthase is known to induce apoptosis(Huang et al., 2000). Caspase genes were upregulated in liver in response toboth acute and chronic methylmercury treatments. Several caspases are knownto be involved in both the initiation of apoptosis (caspase 8,10) and thedestruction of the cells (caspases 3,6,7). Caspase 3 activation in particularhas been found to be associated with methylmercury exposure, leading to apo-ptosis in several types of cells and organs (Nishioku et al., 2000; Robertson &Orrenius, 2000; Usuki et al., 2007). Caspase activation has been shown to be


# 2008 The Authors


part of a cascade starting with calcium ion release into cytosol, leading tocytochrome c release and then caspase activation. In this study and Klaperet al. (2006), several genes associated with calcium ion cascades as well as cyto-chrome c were shown to be differentially regulated with exposure. A tumornecrosis factor (TNF)-like factor, also upregulated in liver in response to acuteexposures, is another inducer of apoptosis in cells.Other studies have indicated that oxidative stress is necessary for apoptosis

to occur (Shenker et al., 2002). However, the results indicate that somethingother than oxidative stress may be stimulating apoptosis at these more environ-mentally realistic concentrations. Methylmercury has been found to trigger celldeath by depleting glutathione in the absence of reactive oxygen species (ROS)overproduction (Gatti et al., 2004). It has also been suggested that MeHgcauses apoptosis through acid activation of endonuclease at lower concentra-tions rather than through ROS (Kuo & Lin-Shiau, 2004). These non-oxidativestress mechanisms of apoptosis induction are supported by the data becausethe authors did not observe alterations in genes indicative of oxidative stress.Alterations in genes involved in the immune system in both gonad and liver

in response to both acute and chronic exposures was observed. Methylmercuryhas been shown to be toxic to the mammalian immune system (Shenker et al.,2000). Antigen presentation genes, and especially the MHC class I and IIgenes, were the most frequently altered within this category. In particular,the MHC class I UBA gene was strongly downregulated in liver under bothacute and chronic exposures (Table VI). Mercury exposure has been shownto lead to immune suppression in fish (Sanchez-Dardon et al., 1999) and is alsoassociated with development of autoimmune disease (Havarinasab et al., 2007).These immune system effects may be related to the previously discussed apo-ptosis effects because immune-related cells undergo apoptosis with methylmer-cury exposure (Shenker et al., 1998).This study demonstrates the utility of microarray studies in developing

hypotheses regarding the impact an environmental contaminant may have onan organism. Specifically, the data presented here point to specific hypothesesregarding the mode of action of methylmercury that differs from those pro-posed previously. While data on individual exposures provide a snapshot ofthe physiological status of an organism, conducting time–course experimentssuch as this one can elucidate the changes that occur over time and the poten-tial for adaptation to a stressor. The microarray data presented in this studywill also eventually be used to conduct a direct comparison of the impactsof this environmental stressor v. several others. Compilations of this type ofdata will eventually point to similarities and differences among stressors withcommon and distinct mechanisms of action increasing the utility of microarraydata for environmental risk assessments.

All research for acute exposures was conducted in accordance to the Columbia Envi-ronmental Research Center (CERC) Animal Welfare Plan and followed procedures andprinciples set out in, ‘Principles for the Utilization and Care of Vertebrate AnimalsUsed in Testing, Research and Training’ (Institute of Laboratory Animal Resources,National Academy Press, 1996). D. Nicks, M. Annis and J. Candrl provided technicalassistance. For chronic exposures, fish in this study were used in accordance with pro-tocols approved by the University of Wisconsin–La Crosse Institutional Animal Care


# 2008 The Authors


and Use Committee. Animals used were treated humanely and with regard for the alle-viation of suffering. This publication was made possible by grant number 2R44ES011882-03A1 from the National Institute of Environmental Health Sciences (NIEHS),National Institutes of Health (NIH). Its contents are solely the responsibility of the au-thors and do not necessarily represent the official view of the NIEHS, National Insti-tute of Health (NIH). This is publication number 483, Great Lakes WATER Institute.

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APPENDIX

I.Significantlyaltered

genes

at

P<

0� 05andgreaterthantw

o-fold

inductionorrepressionin

liver

andgonadin

response

toacute

andchronic

methylm

ercury

exposure

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_52403a

MHC

class

IUFA

gene

7� 74

0� 00308

Liver

Acute

EA_Pp_50897a

Growth

arrest-specific2

5� 77

0� 01190

Liver

Acute

EA_Pp_65939a

GM2gangliosideactivator

5� 48

0� 03350

Liver

Acute

EA_Pp_52584a

Fattyacid-bindingprotein

2,intestinal

4� 89

0� 04650

Liver

Acute

EA_Pp_66600a

Hypotheticalprotein

LOC564481

4� 45

0� 01670

Liver

Acute

EA_Pp_52867a

Hypotheticalprotein

LOC563583

4� 21

0� 03720

Liver

Acute

EA_Pp_56674a

Aldehydeoxidase

13� 65

0� 03160

Liver

Acute

EA_Pp_50101a

Acidphosphatase

2,lysosomal

3� 57

0� 02900

Liver

Acute

EA_Pp_65899a

Adiponectin,C1Q

andcollagen

domain

containing

3� 53

0� 00297

Liver

Acute

EA_Pp_51521a

Unknown

3� 28

0� 02140

Liver

Acute

EA_Pp_65018a

Sim

ilarto

apolipoprotein

B3� 25

0� 04580

Liver

Acute

EA_Pp_52818a

Acylphosphatase

2,muscle

type

3� 22

0� 02030

Liver

Acute

EA_Pp_63727a

Hypotheticalprotein

LOC556805

3� 11

0� 00720

Liver

Acute

EA_Pp_53665a

Unknown

2� 92

0� 00210

Liver

Acute

EA_Pp_54064a

Serpin

peptidase

inhibitor,cladeB,mem

ber

12� 91

0� 00581

Liver

Acute

EA_Pp_66994a

Proenkephalin

2� 87

0� 03960

Liver

Acute

EA_Pp_50568a

All-trans-13,14-dihydroretinolsaturase

2� 78

0� 01920

Liver

Acute

EA_Pp_67372a

Zincfinger

protein

326

2� 76

0� 02570

Liver

Acute

EA_Pp_70949a

Growth

factorretrun-1ceptor-boundprotein

10

2� 66

0� 02720

Liver

Acute

EA_Pp_66631a

Chromosomecondensationprotein

G2� 64

0� 01060

Liver

Acute

EA_Pp_51386a

Hypotheticalprotein

FLJ23554

2� 64

0� 04150

Liver

Acute

EA_Pp_57051a

Myeloid-specificperoxidase

2� 61

0� 03010

Liver

Acute

EA_Pp_59464a

Hypotheticalprotein

LOC572330

2� 61

0� 02970

Liver

Acute

EA_Pp_61487a

Tripartitemotif-containing45

2� 60

0� 01340

Liver

Acute

EA_Pp_68878a

Sim

ilarto

leucocyte

immune-typereceptor3

2� 59

0� 01950

Liver

Acute

EA_Pp_69729a

Sim

ilarto

CG3337-PA

2� 58

0� 03300


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_54254a

Unc4� 1

homeobox

2� 57

0� 01250

Liver

Acute

EA_Pp_65550a

Proopiomelanocortin

A2� 52

0� 00252

Liver

Acute

EA_Pp_68886a

Hypotheticalprotein

LOC566646

2� 44

0� 02560

Liver

Acute

EA_Pp_59627a

Oestrogen-relatedreceptorgamma

2� 39

0� 03900

Liver

Acute

EA_Pp_55110a

Phosphotriesterase

related

2� 37

0� 00318

Liver

Acute

EA_Pp_52527a

Mast

cellprotease

42� 34

0� 03110

Liver

Acute

EA_Pp_53617a

Novel

protein

similarto

vertebrate

NIM

A-related

expressed

kinase

12� 31

0� 03520

Liver

Acute

EA_Pp_54338a

Nurim

2� 30

0� 02590

Liver

Acute

EA_Pp_53526a

Hypotheticalprotein

LOC569467

2� 28

0� 03040

Liver

Acute

EA_Pp_55951a

Zgc:77479

2� 27

0� 00264

Liver

Acute

EA_Pp_50103a

Insulin-likegrowth

factor2precursor

2� 27

0� 02030

Liver

Acute

EA_Pp_57138a

Unknown

2� 23

0� 04400

Liver

Acute

EA_Pp_60398a

Protein

tyrosinephosphatase,receptortype,

G2� 22

0� 01750

Liver

Acute

EA_Pp_51958a

RIK

EN

cDNA

1700029F09gene

2� 20

0� 00827

Liver

Acute

EA_Pp_68014a

RIK

EN

cDNA

1700088E04gene

2� 13

0� 00111

Liver

Acute

EA_Pp_67913a

Zgc:123068

2� 10

0� 04840

Liver

Acute

EA_Pp_68183a

RIK

EN

cDNA

2210411K11gene

2� 09

0� 04320

Liver

Acute

EA_Pp_50915a

InhibitorofDNA-binding4,dominantnegative

helix-loop-helix

protein

2� 09

0� 03370

Liver

Acute

EA_Pp_66948a

Zgc:56701

2� 02

0� 04190

Liver

Acute

EA_Pp_60544a

Phospholipase

Dfamily,mem

ber

42� 02

0� 04920

Liver

Acute

EA_Pp_70610a

Exostoses-like2

2� 01

0� 00662

Liver

Acute

EA_Pp_69615a

Unknown

2� 00

0� 00861

Liver

Acute

EA_Pp_69301a

ENSANGP00000028549

1� 98

0� 03770

Liver

Acute

EA_Pp_52687a

GULP,engulfmentadaptorPTB

domain-containing1

1� 97

0� 03120

Liver

Acute

EA_Pp_51565a

Transm

embrane7superfamilymem

ber

1a

1� 96

0� 02030


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_67245a

Centrosomalprotein

164kDa

1� 95

0� 03380

Liver

Acute

EA_Pp_63147a

Dystrophin

1� 94

0� 00157

Liver

Acute

EA_Pp_50210a

Sim

ilarto

zincfinger,MYND

domain-containing12

1� 93

0� 04770

Liver

Acute

EA_Pp_50825a

Hypotheticalprotein

MGC10986

1� 92

0� 00834

Liver

Acute

EA_Pp_57692a

Unknown

1� 90

0� 02110

Liver

Acute

EA_Pp_64935a

Hypotheticalprotein

LOC569091

1� 90

0� 02160

Liver

Acute

EA_Pp_62686a

Adenosinedeaminase,RNA-specific

1� 89

0� 04990

Liver

Acute

EA_Pp_57311a

Unknown

1� 89

0� 03960

Liver

Acute

EA_Pp_69450a

Claudin

H1� 89

0� 02370

Liver

Acute

EA_Pp_57191a

RIK

EN

cDNA

4933424C13gene

1� 88

0� 03620

Liver

Acute

EA_Pp_62464a

Unknown

1� 88

0� 01410

Liver

Acute

EA_Pp_66887a

RIK

EN

cDNA

3632451O06gene

1� 87

0� 02220

Liver

Acute

EA_Pp_61703a

Genemodel

1362,

1� 85

0� 03850

Liver

Acute

EA_Pp_54395a

Unknown

1� 85

0� 01490

Liver

Acute

EA_Pp_60556a

Hypotheticalprotein

LOC553370

1� 85

0� 04230

Liver

Acute

EA_Pp_60144a

Wu:fi33g05

1� 82

0� 04590

Liver

Acute

EA_Pp_55055a

MGC80698protein

1� 81

0� 02600

Liver

Acute

EA_Pp_51662a

Hypotheticalprotein

FLJ35630

1� 81

0� 03360

Liver

Acute

EA_Pp_69423a

MonopolarSpindle

11� 80

0� 03620

Liver

Acute

EA_Pp_61038a

[Pro2]-somatostatinprecursor

1� 79

0� 01150

Liver

Acute

EA_Pp_66292a

Sim

ilarto

cyclin-dependentkinase

inhibitor3

1� 77

0� 00359

Liver

Acute

EA_Pp_60608a

Unknown

1� 74

0� 00191

Liver

Acute

EA_Pp_53184a

Phosphoribosylpyrophosphate

synthetase-associated

protein

11� 74

0� 04080

Liver

Acute

EA_Pp_51228a

Adenylate

kinase

51� 74

0� 02020

Liver

Acute

EA_Pp_58305a

Sim

ilarto

osteocrin

1� 73

0� 04890

Liver

Acute

EA_Pp_68176a

DNA

segment,Chr6,WayneState

University

163,expressed

1� 73

0� 00845


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_71091a

Sim

ilarto

plateletendothelialcelladhesion

molecule

precursor

1� 72

0� 01830

Liver

Acute

EA_Pp_51731a

Unknown

1� 68

0� 00690

Liver

Acute

EA_Pp_53292a

Methionineadenosyltransferase

I,alpha

1� 68

0� 01630

Liver

Acute

EA_Pp_61233a

HypotheticalProtein

LOC558249

1� 68

0� 04440

Liver

Acute

EA_Pp_67506a

Sim

ilarto

developmentallyregulatedRNA-binding

protein

11� 67

0� 03150

Liver

Acute

EA_Pp_58858a

KIA

A1333

1� 66

0� 02210

Liver

Acute

EA_Pp_55642a

Barren

homologue

1� 66

0� 03850

Liver

Acute

EA_Pp_62192a

CG33248-PA

1� 66

0� 01740

Liver

Acute

EA_Pp_57171a

59-nucleotidase,cytosolicII

1� 65

0� 01760

Liver

Acute

EA_Pp_56374a

Midkine-relatedgrowth

factor

1� 64

0� 01440

Liver

Acute

EA_Pp_56718a

Caspase


1� 64

0� 02440

Liver

Acute

EA_Pp_51750a

C1qdomain-containing2

1� 63

0� 02300

Liver

Acute

EA_Pp_69455a

Zgc:77234

1� 63

0� 04150

Liver

Acute

EA_Pp_69271a

SH2domain-containing5

1� 63

0� 00644

Liver

Acute

EA_Pp_54307a

UDP-G

lcNAc:betaGalbeta-1,3-N

-acetylglucosaminyl-

transferase

41� 63

0� 00523

Liver

Acute

EA_Pp_57032a

Phosphatase

andactin

regulator1

1� 63

0� 04610

Liver

Acute

EA_Pp_66481a

Zgc:112315

1� 62

0� 04490

Liver

Acute

EA_Pp_58304a

Integrinbeta-1

1� 62

0� 02340

Liver

Acute

EA_Pp_59880a

Chem

okinereceptor9

1� 59

0� 00880

Liver

Acute

EA_Pp_67243a

Zgc:55418

1� 58

0� 00868

Liver

Acute

EA_Pp_54287a

Matrix

metallopeptidase

17

1� 58

0� 03030

Liver

Acute

EA_Pp_52704a

PDZ-bindingkinase

1� 57

0� 00398

Liver

Acute

EA_Pp_50993a

Chromosome16open

readingframe52

1� 57

0� 03340

Liver

Acute

EA_Pp_64537a

Sim

ilarto

ectonucleotidepyrophosphatase/

phosphodiesterase

51� 57

0� 02120


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_50620a

Ictacalcin

1� 56

0� 02220

Liver

Acute

EA_Pp_67350a

Unknown

1� 56

0� 02670

Liver

Acute

EA_Pp_56936a

Lectin,galactoside-binding,soluble,1-like2

1� 56

0� 01190

Liver

Acute

EA_Pp_67011a

Sim

ilarto

epithelialprotein

lost

inneoplasm

1� 55

0� 03690

Liver

Acute

EA_Pp_53806a

TRB-2

protein

1� 53

0� 00595

Liver

Acute

EA_Pp_57549a

Proline–serine–threoninephosphatase-interacting

protein

11� 52

0� 03750

Liver

Acute

EA_Pp_69997a

T-cellreceptoralphaconstant

1� 52

0� 04890

Liver

Acute

EA_Pp_66643a

Unknown

1� 52

0� 00573

Liver

Acute

EA_Pp_59022a

Unknown

1� 52

0� 01710

Liver

Acute

EA_Pp_69420a

Activatingtranscriptionfactor3

1� 51

0� 04860

Liver

Acute

EA_Pp_58919a

RAB40B,mem

ber

RASoncogenefamily

1� 51

0� 04580

Liver

Acute

EA_Pp_57145a

Unknown

1� 51

0� 00275

Liver

Acute

EA_Pp_55551a

Deoxythymidylate

kinase

1� 51

0� 02540

Liver

Acute

EA_Pp_53858a

Sim

ilarto

serine–threonine-protein

kinase

PLK2

1� 51

0� 02530

Liver

Acute

EA_Pp_64484a

Headcase

homologue

1� 51

0� 04050

Liver

Acute

EA_Pp_57123a

V-rosUR2sarcomavirusoncogenehomologue1

1� 49

0� 04330

Liver

Acute

EA_Pp_57810a

Sim

ilarto

rhoguaninenucleotideexchangefactor6

1� 49

0� 04410

Liver

Acute

EA_Pp_69669a

Zgc:65861

1� 48

0� 04990

Liver

Acute

EA_Pp_70061a

Sim

ilarto

RIK

EN

cDNA

D330028D13

1� 48

0� 04700

Liver

Acute

EA_Pp_53756a

Unknown

1� 48

0� 01210

Liver

Acute

EA_Pp_59567a

DNA

methyltransferase

3B

1� 47

0� 03290

Liver

Acute

EA_Pp_71148a

Jumonjidomain-containing3

1� 46

0� 00591

Liver

Acute

EA_Pp_51022a

Unknown

1� 46

0� 03040

Liver

Acute

EA_Pp_58490a

SRY-box4b

1� 45

0� 04130

Liver

Acute

EA_Pp_52045a

Unknown

1� 45

0� 04630

Liver

Acute

EA_Pp_59115a

Orthopaedic

homologue

1� 44

0� 02110


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_59872a

KIA

A2022protein

1� 44

0� 02080

Liver

Acute

EA_Pp_55041a

Fidgetin

1� 42

0� 04530

Liver

Acute

EA_Pp_69408a

Unknown

1� 42

0� 03880

Liver

Acute

EA_Pp_63086a

Acetyl-coenzyme-A

carboxylase

beta

1� 42

0� 04620

Liver

Acute

EA_Pp_51062a

UBX

domain-containing1

1� 41

0� 04790

Liver

Acute

EA_Pp_62456a

Zgc:64013

1� 41

0� 03790

Liver

Acute

EA_Pp_65702a

Unknown

1� 41

0� 02160

Liver

Acute

EA_Pp_60005a

Sim

ilarto

S-100Pprotein

1� 41

0� 00150

Liver

Acute

EA_Pp_64684a

Unknown

1� 39

0� 04890

Liver

Acute

EA_Pp_66657a

PHD

finger

protein

21B

1� 38

0� 02510

Liver

Acute

EA_Pp_51153a

C-typelectin

domain

family3,mem

ber

B1� 37

0� 02000

Liver

Acute

EA_Pp_63889a

Nuclearprotein

11� 37

0� 00677

Liver

Acute

EA_Pp_67978a

Lysozyme

1� 36

0� 02050

Liver

Acute

EA_Pp_62188a

ELOVLfamilymem

ber

5,elongationoflong-chain

fattyacids

1� 36

0� 03330

Liver

Acute

EA_Pp_68781a

ATG4autophagy-related4homologueD

1� 36

0� 00530

Liver

Acute

EA_Pp_63739a

Zincfinger

protein

509

1� 36

0� 03340

Liver

Acute

EA_Pp_61275a

Zgc:91813

1� 35

0� 01800

Liver

Acute

EA_Pp_65986a

CD3antigen,zeta

polypeptide

1� 35

0� 02970

Liver

Acute

EA_Pp_53400a

Unknown

1� 35

0� 04320

Liver

Acute

EA_Pp_54510a

Unknown

1� 34

0� 04510

Liver

Acute

EA_Pp_55035a

Arrestindomain-containing2

1� 34

0� 02090

Liver

Acute

EA_Pp_61860a

CDC42effectorprotein

11� 34

0� 01160

Liver

Acute

EA_Pp_63838a

Zgc:92796

1� 33

0� 02010

Liver

Acute

EA_Pp_59763a

SMC4structuralmaintenance

ofchromosomes

4-like1

1� 32

0� 03620

Liver

Acute

EA_Pp_65544a

Sim

ilarto

RIK

EN

cDNA

2310044G17

1� 32

0� 04260

Liver

Acute

EA_Pp_58910a

Sim

ilarto

UPF0143protein

C14orf1

1� 31

0� 01120

Liver

Acute

EA_Pp_64207a

Kinesin

familymem

ber

11

1� 31

0� 02550


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_57980a

Uracil-DNA

glycosylase

1� 31

0� 01540

Liver

Acute

EA_Pp_69329a

Chromosome20open

readingframe82

1� 31

0� 01390

Liver

Acute

EA_Pp_66619a

Chromosome14open

readingframe93

1� 30

0� 03870

Liver

Acute

EA_Pp_63310a

Sim

ilarto

interferon-inducible

protein

Gig2

1� 29

0� 01790

Liver

Acute

EA_Pp_59908a

Unknown

1� 29

0� 04090

Liver

Acute

EA_Pp_70704a

Hypotheticalprotein

BC008326

1� 29

0� 01650

Liver

Acute

EA_Pp_60596a

Tumourrejectionantigen

11� 28

0� 04960

Liver

Acute

EA_Pp_53733a

Unknown

1� 28

0� 00092

Liver

Acute

EA_Pp_55788a

Dynein,axonem

al,heavypolypeptide9

1� 28

0� 03610

Liver

Acute

EA_Pp_54000a

Hypotheticalprotein

LOC407707

1� 28

0� 04510

Liver

Acute

EA_Pp_50638a

Intraflagellartransport

81homologue

1� 28

0� 00455

Liver

Acute

EA_Pp_59274a

Pterin-4

alpha-carbinolaminedehydratase/dim

erization

cofactorofhepatocyte

nuclearfactor1alpha-2

1� 27

0� 01550

Liver

Acute

EA_Pp_70600a

Tumournecrosisfactor,alpha-inducedprotein

81� 27

0� 04110

Liver

Acute

EA_Pp_62569a

Zincfinger,CCHC

domain-containing7-like

1� 26

0� 03920

Liver

Acute

EA_Pp_57065a

Catechol-O-m

ethyltransferase

1� 26

0� 02420

Liver

Acute

EA_Pp_59106a

Sim

ilarto

neuron-glia-C

AM-relatedcelladhesionmolecule

1� 25

0� 00512

Liver

Acute

EA_Pp_52115a

Expressed

sequence

AI847670

1� 25

0� 03860

Liver

Acute

EA_Pp_61882a

RIK

EN

cDNA

2410089E03gene

1� 24

0� 03590

Liver

Acute

EA_Pp_62565a

CathepsinO

1� 24

0� 02240

Liver

Acute

EA_Pp_51815a

Sim

ilarto

alveolin

1� 23

0� 01590

Liver

Acute

EA_Pp_53680a

Sim

ilarto

synaptotagmin-likeprotein

2-a

delta

2S-I

1� 23

0� 01180

Liver

Acute

EA_Pp_52857a

RAB18,mem

ber

RASoncogenefamily

1� 22

0� 02360

Liver

Acute

EA_Pp_51666a

Suppressorofcytokinesignalling3

1� 22

0� 04040

Liver

Acute

EA_Pp_51567a

MyosinVC

1� 21

0� 00026

Liver

Acute

EA_Pp_58581a

Sim

ilarto

dualspecificity

testis-specificprotein

kinase

21� 21

0� 01640

Liver

Acute

EA_Pp_53108a

WD

repeatdomain

23

1� 20

0� 00364


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_56322a

Vinculin

1� 20

0� 02520

Liver

Acute

EA_Pp_50279a

SH3multiple

domains1

1� 20

0� 04770

Liver

Acute

EA_Pp_52048a

Si:busm

1-228j01� 6

1� 20

0� 03640

Liver

Acute

EA_Pp_60698a

Dynamin

21� 20

0� 04000

Liver

Acute

EA_Pp_59160a

XIA

P-associatedfactor1

1� 19

0� 03650

Liver

Acute

EA_Pp_55531a

Bonemorphogenetic

protein

receptor,type1b

1� 19

0� 04380

Liver

Acute

EA_Pp_70785a

Solute

carrierfamily27,mem

ber

21� 18

0� 00312

Liver

Acute

EA_Pp_56103a

Developmentanddifferentiationenhancing

1� 18

0� 02190

Liver

Acute

EA_Pp_63788a

Sim

ilarto

RPGT208

1� 18

0� 03130

Liver

Acute

EA_Pp_52766a

Zgc:91856

1� 17

0� 02940

Liver

Acute

EA_Pp_54226a

Unknown

1� 17

0� 04740

Liver

Acute

EA_Pp_70872a

Unknown

1� 17

0� 04380

Liver

Acute

EA_Pp_69175a

Vav3oncogene

1� 17

0� 04140

Liver

Acute

EA_Pp_65015a

Unknown

1� 16

0� 00978

Liver

Acute

EA_Pp_65369a

Sim

ilarto

LOC398683protein

1� 16

0� 00384

Liver

Acute

EA_Pp_58188a

Zgc:92582

1� 16

0� 00863

Liver

Acute

EA_Pp_59518a

Hypotheticalprotein

DKFZp564O0523

1� 16

0� 04260

Liver

Acute

EA_Pp_54351a

Isochorism

atase

domain-containing2

1� 16

0� 01720

Liver

Acute

EA_Pp_53368a

Tyrosinekinase

receptor1

1� 16

0� 01550

Liver

Acute

EA_Pp_58700a

Unknown

1� 16

0� 03280

Liver

Acute

EA_Pp_51881a

DNA

primase,P49subunit

1� 16

0� 00594

Liver

Acute

EA_Pp_51286a

Unknown

1� 15

0� 01570

Liver

Acute

EA_Pp_56040a

Interleukin

12B

1� 15

0� 01990

Liver

Acute

EA_Pp_51542a

Potassium

channel

tetramerizationdomain-containing7

1� 15

0� 04720

Liver

Acute

EA_Pp_56149a

Periodhomologue4

1� 14

0� 02310

Liver

Acute

EA_Pp_63438a

Sim

ilarto

novel

Rasfamilymem

ber

1� 14

0� 02100

Liver

Acute

EA_Pp_51764a

Sim

ilarto

protein

kinase

C,Eta

type

1� 14

0� 03930


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_56263a

NCK-associatedprotein

1-like

1� 13

0� 02570

Liver

Acute

EA_Pp_56408a

SWI–SNFrelated,Matrix

associated,actin-dependent

regulatorofchromatin,subfamilyA,Mem

ber

21� 13

0� 04370

Liver

Acute

EA_Pp_61983a

F-boxonly

protein

31� 12

0� 03610

Liver

Acute

EA_Pp_57015a

RIK

EN

cDNA

1300007F04gene

1� 12

0� 04870

Liver

Acute

EA_Pp_55990a

Sim

ilarto

inositol1,4,5-trisphosphate

3-kinase

A1� 11

0� 03340

Liver

Acute

EA_Pp_64801a

Hypotheticalprotein

LOC568178

1� 11

0� 03470

Liver

Acute

EA_Pp_67289a

ForkheadboxP1

1� 11

0� 00283

Liver

Acute

EA_Pp_66636a

Hypotheticalprotein

LOC556846

1� 10

0� 01730

Liver

Acute

EA_Pp_67895a

Unknown

1� 09

0� 01790

Liver

Acute

EA_Pp_61891a

Zgc:66026

1� 09

0� 03600

Liver

Acute

EA_Pp_51123a

Unknown

1� 09

0� 02420

Liver

Acute

EA_Pp_67583a

Tudordomain-containing6

1� 08

0� 04610

Liver

Acute

EA_Pp_56857a

Hypotheticalprotein

LOC559503

1� 08

0� 04500

Liver

Acute

EA_Pp_66155a

Sim

ilarto

IQmotif-containingE

1� 08

0� 01670

Liver

Acute

EA_Pp_53615a

Unknown

1� 08

0� 03120

Liver

Acute

EA_Pp_65090a

Sim

ilarto

LOC407656protein

1� 08

0� 03170

Liver

Acute

EA_Pp_51967a

Zgc:114097

1� 08

0� 02680

Liver

Acute

EA_Pp_55764a

BPLF1

1� 07

0� 01740

Liver

Acute

EA_Pp_53996a

Unknown

1� 07

0� 04090

Liver

Acute

EA_Pp_53994a

Poly

polymerase

family,mem

ber

41� 06

0� 03310

Liver

Acute

EA_Pp_67377a

Ringfinger

protein

144

1� 06

0� 02850

Liver

Acute

EA_Pp_66926a

Unknown

1� 06

0� 03940

Liver

Acute

EA_Pp_50607a

MAD,mothersagainst

decapentaplegic

homologue3b

1� 05

0� 03790

Liver

Acute

EA_Pp_51635a

Zgc:55982

1� 05

0� 01870

Liver

Acute

EA_Pp_50123a

Phosphofructokinase,liver

1� 04

0� 00889

Liver

Acute

EA_Pp_59113a

Ets

homologousfactor

1� 04

0� 02030


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_56225a

ADAM

metallopeptidase

domain

71� 03

0� 03300

Liver

Acute

EA_Pp_55330a

Zgc:77121

1� 03

0� 01170

Liver

Acute

EA_Pp_67835a

Zincfinger,CCHC

domain-containing7-like

1� 03

0� 01350

Liver

Acute

EA_Pp_64571a

Clusterin-associatedprotein

11� 03

0� 01040

Liver

Acute

EA_Pp_64872a

Unknown

1� 03

0� 02590

Liver

Acute

EA_Pp_70496a

Inhibitorofgrowth

family,mem

ber

31� 03

0� 01530

Liver

Acute

EA_Pp_55553a

Wu:fc23f06

1� 03

0� 03590

Liver

Acute

EA_Pp_53669a

Leprecan1

1� 02

0� 01830

Liver

Acute

EA_Pp_50910a

Sim

ilarto

MGC81165protein

1� 02

0� 03650

Liver

Acute

EA_Pp_52004a

MyosinIX

B1� 01

0� 04680

Liver

Acute

EA_Pp_69578a

Sim

ilarto

tumournecrosisfactorligandsuperfamily

mem

ber

14

1� 01

0� 04400

Liver

Acute

EA_Pp_61562a

Fibroblast

growth

factor12

1� 00

0� 04690

Liver

Acute

EA_Pp_50469a

RAN

GTPase-activatingprotein

1�1� 00

0� 00763

Liver

Acute

EA_Pp_70638a

Mitochondrialribosomalprotein

L18

�1� 01

0� 02320

Liver

Acute

EA_Pp_64157a

Peter

Panhomologue

�1� 01

0� 02720

Liver

Acute

EA_Pp_58403a

Protein

disulphideisomerase

familyA,mem

ber

5�1� 01

0� 03300

Liver

Acute

EA_Pp_68422a

Importin

9�1� 01

0� 01180

Liver

Acute

EA_Pp_68212a

Signalrecognitionparticle

�1� 01

0� 00075

Liver

Acute

EA_Pp_68788a

DEAD

boxpolypeptide27

�1� 01

0� 02710

Liver

Acute

EA_Pp_53190a

DEAD

boxpolypeptide18

�1� 02

0� 01020

Liver

Acute

EA_Pp_66463a

ATPase,Hþ

transporting,lysosomal70kDa,

V1subunitA

�1� 02

0� 01640

Liver

Acute

EA_Pp_54495a

Biliverdin

reductase

A�1� 02

0� 04510

Liver

Acute

EA_Pp_56666a

Mitochondrialtranslationalrelease

factor1-like

�1� 03

0� 02920

Liver

Acute

EA_Pp_63879a

Coatomer

protein

complex,subunitbeta

�1� 03

0� 04070

Liver

Acute

EA_Pp_59307a

Ubiquitin-fold

modifier

1�1� 03

0� 01200


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_63623a

Thioredoxin

domain-containing5

�1� 03

0� 02960

Liver

Acute

EA_Pp_64670a

Sideroflexin

2�1� 03

0� 03040

Liver

Acute

EA_Pp_65238a

Presenilin

associated,rhomboid-like

�1� 03

0� 04620

Liver

Acute

EA_Pp_58141a

Heterogeneousnuclearribonucleoprotein

A–B

�1� 04

0� 02540

Liver

Acute

EA_Pp_62493a

Zgc:77708

�1� 05

0� 02130

Liver

Acute

EA_Pp_61803a

Loss

ofheterozygosity,12,chromosomalregion1

�1� 06

0� 00804

Liver

Acute

EA_Pp_56222a

Zgc:85675

�1� 06

0� 04130

Liver

Acute

EA_Pp_60632a

Cytochrome

b-561domain-containing1

�1� 06

0� 00563

Liver

Acute

EA_Pp_70769a

Pleiotropic

regulator1

�1� 06

0� 00693

Liver

Acute

EA_Pp_59961a

RAN-bindingprotein

5�1� 06

0� 00728

Liver

Acute

EA_Pp_56734a

Sim

ilarto

nucleoprotein

TPR

�1� 06

0� 04460

Liver

Acute

EA_Pp_51899a

Bromodomain

adjacentto

zincfinger

domain,1A

�1� 06

0� 00195

Liver

Acute

EA_Pp_58034a

Selenoprotein

�1� 06

0� 01450

Liver

Acute

EA_Pp_64389a

Nucleoporin188kDa

�1� 06

0� 01500

Liver

Acute

EA_Pp_68538a

Interferon-relateddevelopmentalregulator1

�1� 06

0� 02090

Liver

Acute

EA_Pp_59743a

Adenylosuccinate

synthase

�1� 06

0� 02180

Liver

Acute

EA_Pp_63289a


1homologue

�1� 07

0� 00818

Liver

Acute

EA_Pp_62358a

Attractin

�1� 07

0� 02410

Liver

Acute

EA_Pp_50235a

Zgc:65944

�1� 07

0� 04480

Liver

Acute

EA_Pp_58313a

RNA-bindingprotein

S1,serine-rich

domain

�1� 07

0� 03690

Liver

Acute

EA_Pp_64852a

Zgc:56513

�1� 07

0� 01270

Liver

Acute

EA_Pp_65859a

Karyopherin

alpha3

�1� 08

0� 01070

Liver

Acute

EA_Pp_60611a

Componentofoligomeric

Golgicomplex7

�1� 08

0� 04770

Liver

Acute

EA_Pp_55364a

Zgc:56488

�1� 08

0� 00469

Liver

Acute

EA_Pp_62142a

Unknown

�1� 08

0� 04030

Liver

Acute

EA_Pp_54154a

Methylcrotonoyl-coenzyme-A

carboxylase

2�1� 09

0� 03140

Liver

Acute

EA_Pp_57030a

Zgc:100813

�1� 09

0� 04090


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_53791a

Valyl-tR

NA

synthetase

�1� 09

0� 04630

Liver

Acute

EA_Pp_50489a

Proteasomesubunit,alphatype2

�1� 09

0� 01540

Liver

Acute

EA_Pp_70292a

SET

AndMYND

domain-containing2

�1� 09

0� 04560

Liver

Acute

EA_Pp_56733a

RhofamilyGTPase

1�1� 09

0� 01790

Liver

Acute

EA_Pp_50154a

Hypotheticalprotein

LOC402823

�1� 09

0� 03490

Liver

Acute

EA_Pp_65800a

Polymerase

IIpolypeptideC,33kDa

�1� 09

0� 04050

Liver

Acute

EA_Pp_64525a

RIK

EN

cDNA

4921521J11gene

�1� 10

0� 02710

Liver

Acute

EA_Pp_53753a

Cyclin-dependentkinase

5,regulatory

subunit2

�1� 10

0� 00147

Liver

Acute

EA_Pp_61421a

Zgc:63733

�1� 10

0� 03760

Liver

Acute

EA_Pp_60031a

Williams-Beurensyndromechromosomeregion16

�1� 10

0� 04910

Liver

Acute

EA_Pp_50557a

Glycolipid

transfer

protein

�1� 10

0� 02050

Liver

Acute

EA_Pp_67163a

Sec31phomologue

�1� 10

0� 02630

Liver

Acute

EA_Pp_68715a

HEAT

repeatcontaining1

�1� 11

0� 00617

Liver

Acute

EA_Pp_68834a

Sim

ilarto

tubulintyrosineligase-likeprotein

4�1� 11

0� 02060

Liver

Acute

EA_Pp_59261a

RIK

EN

cDNA

1110039B18gene

�1� 11

0� 02360

Liver

Acute

EA_Pp_63702a

Thioredoxin

domain-containing12

�1� 11

0� 02540

Liver

Acute

EA_Pp_55039a

Im:6893299

�1� 11

0� 04520

Liver

Acute

EA_Pp_60029a

Actin-relatedprotein

2–3complex,subunit1A,41kDa

�1� 11

0� 01940

Liver

Acute

EA_Pp_56641a

Sec1familydomain-containing1

�1� 11

0� 04530

Liver

Acute

EA_Pp_56486a

Succinate

dehydrogenase

complex,subunitB,

ironsulphur

�1� 12

0� 00126

Liver

Acute

EA_Pp_70702a

Unknown

�1� 12

0� 01570

Liver

Acute

EA_Pp_61074a

tRNA


2homologue

�1� 12

0� 03390

Liver

Acute

EA_Pp_64819a

MediatorofRNA

polymerase

IItranscription,subunit25

homologue

�1� 12

0� 03900

Liver

Acute

EA_Pp_59107a

Adaptorprotein

complexAP-1,Mu2subunit

�1� 12

0� 01370


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_55580a

DNA

segment,Chr1,Brigham

andWomen’sgenetics

0491expressed

�1� 12

0� 04160

Liver

Acute

EA_Pp_50256a

SIL

1homologue,

endoplasm

icreticulum

chaperone

�1� 13

0� 00867

Liver

Acute

EA_Pp_55087a

WD

repeatdomain

75

�1� 13

0� 00176

Liver

Acute

EA_Pp_57963a

Superkillerviralicidic

activity2-like2

�1� 13

0� 00428

Liver

Acute

EA_Pp_69685a

RAD1homologue

�1� 13

0� 02420

Liver

Acute

EA_Pp_63713a

Sim

ilarto

Kelch

domain-containing4

�1� 13

0� 04160

Liver

Acute

EA_Pp_54589a

WD

repeatdomain

39

�1� 13

0� 02750

Liver

Acute

EA_Pp_61433a

TruBpseudouridinesynthase

homologue1

�1� 13

0� 04530

Liver

Acute

EA_Pp_62429a

Hypotheticalprotein

LOC559491

�1� 14

0� 02960

Liver

Acute

EA_Pp_50648a

ImmunoglobulinMu-bindingprotein

2�1� 14

0� 03150

Liver

Acute

EA_Pp_70444a

KIA

A0310

�1� 14

0� 04480

Liver

Acute

EA_Pp_52817a

Retinoic

acid-induced12

�1� 14

0� 01620

Liver

Acute

EA_Pp_61536a

DAZ-associatedprotein

1�1� 14

0� 03180

Liver

Acute

EA_Pp_57181a

Zgc:65781

�1� 15

0� 02150

Liver

Acute

EA_Pp_54001a

EBNA1-bindingprotein

2-like

�1� 15

0� 01700

Liver

Acute

EA_Pp_51776a

WW

domain-containingoxidoreductase

�1� 15

0� 01740

Liver

Acute

EA_Pp_61709a

Zincfinger,ZZ-typewithEF-handdomain

1�1� 15

0� 03070

Liver

Acute

EA_Pp_69396a

Leucine-rich

repeats

anddeath

domain

containing

�1� 15

0� 04240

Liver

Acute

EA_Pp_61857a

Sim

ilarto

EGLninehomologue2isoform

1�1� 16

0� 01310

Liver

Acute

EA_Pp_55849a

Dehydrogenase

E1andtransketolase

domain-containing1

�1� 16

0� 02280

Liver

Acute

EA_Pp_61061a

Calreticulinlike

�1� 16

0� 02740

Liver

Acute

EA_Pp_54985a

Vpr-bindingprotein

�1� 16

0� 03980

Liver

Acute

EA_Pp_54876a

Hypotheticalprotein

LOC559385

�1� 16

0� 00179

Liver

Acute

EA_Pp_58900a

Zgc:77010

�1� 16

0� 03320

Liver

Acute

EA_Pp_50415a

SEC63like

�1� 16

0� 04480

Liver

Acute

EA_Pp_66726a

Zgc:66416

�1� 17

0� 03540


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_52169a

RNA

polymerase

1-2

�1� 17

0� 00003

Liver

Acute

EA_Pp_50547a

Solute

carrierfamily20,mem

ber

2�1� 17

0� 00609

Liver

Acute

EA_Pp_57340a

Sim

ilarto

hypotheticalUPF0327protein

�1� 17

0� 03440

Liver

Acute

EA_Pp_64864a

Transm

embrane9superfamilymem

ber

1�1� 17

0� 02550

Liver

Acute

EA_Pp_66907a

ENSANGP00000019596

�1� 17

0� 03990

Liver

Acute

EA_Pp_64205a

Transcriptionterm

inationfactor,RNA

polymerase

II�1� 18

0� 02860

Liver

Acute

EA_Pp_66169a

Wu:fx03e08

�1� 18

0� 03690

Liver

Acute

EA_Pp_54258a

Cystathionine-beta-synthase

�1� 18

0� 04550

Liver

Acute

EA_Pp_69247a

82-kD

FMRP-interactingprotein

�1� 18

0� 04750

Liver

Acute

EA_Pp_59317a

Zgc:92656

�1� 18

0� 04970

Liver

Acute

EA_Pp_53035a

Lactationelevated1

�1� 18

0� 01690

Liver

Acute

EA_Pp_50983a

Ubiquitin-specificpeptidase

49

�1� 18

0� 02650

Liver

Acute

EA_Pp_53887a

Sim

ilarto

cytoplasm

icnuclearfactorofactivatedT-cell4

�1� 18

0� 01430

Liver

Acute

EA_Pp_65454a

Hypotheticalprotein

FLJ20272

�1� 18

0� 02220

Liver

Acute

EA_Pp_63176a

Chloridechannel

3�1� 18

0� 03210

Liver

Acute

EA_Pp_61554a

Breast

carcinomaamplified

sequence

2�1� 18

0� 04530

Liver

Acute

EA_Pp_66371a

Dolichylpyrophosphate

phosphatase

1�1� 18

0� 04660

Liver

Acute

EA_Pp_55886a

Single-stranded

DNA-bindingprotein

1�1� 19

0� 02650

Liver

Acute

EA_Pp_70387a

MalignantT-cellamplified

sequence

1�1� 19

0� 03470

Liver

Acute

EA_Pp_64773a

Unknown

�1� 19

0� 00651

Liver

Acute

EA_Pp_63672a

Zgc:73311

�1� 19

0� 01940

Liver

Acute

EA_Pp_51875a

Sim

ilarto

Rrp8plike

�1� 19

0� 00773

Liver

Acute

EA_Pp_65035a

UTP14,U3sm

allnucleolarribonucleoprotein,homologueB

�1� 19

0� 01080

Liver

Acute

EA_Pp_53674a

KIA

A0090

�1� 19

0� 03740

Liver

Acute

EA_Pp_56084a

Torsin

family1,mem

ber

A�1� 20

0� 04940

Liver

Acute

EA_Pp_65681a

Hypotheticalprotein

FLJ20485

�1� 20

0� 04430

Liver

Acute

EA_Pp_63395a

Hypotheticalprotein

FLJ13089

�1� 20

0� 02330


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_58442a

Zgc:63524

�1� 20

0� 02610

Liver

Acute

EA_Pp_67365a

Death-associatedprotein

3�1� 21

0� 02600

Liver

Acute

EA_Pp_61066a

Glutamate

oxaloacetate

transaminase

1,soluble

�1� 21

0� 03370

Liver

Acute

EA_Pp_58375a

CDC23

�1� 21

0� 03510

Liver

Acute

EA_Pp_57186a

Adaptor-relatedprotein

complex1,Mu1subunit

�1� 21

0� 03970

Liver

Acute

EA_Pp_52170a

Im:6895552

�1� 21

0� 04100

Liver

Acute

EA_Pp_61735a

Zgc:56683

�1� 21

0� 04840

Liver

Acute

EA_Pp_54998a

Zgc:56317

�1� 22

0� 04850

Liver

Acute

EA_Pp_60869a

FLJ20859gene

�1� 22

0� 03890

Liver

Acute

EA_Pp_50216a

MYC-inducednuclearantigen

�1� 22

0� 03980

Liver

Acute

EA_Pp_50246a

Sim

ilarto

myotubularin

�1� 22

0� 04480

Liver

Acute

EA_Pp_51768a

DEAD

boxpolypeptide49

�1� 23

0� 04510

Liver

Acute

EA_Pp_55403a

Der1-likedomain

family,mem

ber

2�1� 23

0� 04200

Liver

Acute

EA_Pp_58551a

Sim

ilarto

bromoadjacenthomologydomain-containing1

�1� 24

0� 02110

Liver

Acute

EA_Pp_63877a

Smallnuclearribonucleoprotein

D3polypeptide18kDa

�1� 24

0� 02500

Liver

Acute

EA_Pp_50222a

Transm

embraneprotein

32

�1� 24

0� 03540

Liver

Acute

EA_Pp_67016a

Tumourrejectionantigen

Gp96

�1� 25

0� 00746

Liver

Acute

EA_Pp_59884a

Solute

carrierfamily35,mem

ber

E1

�1� 25

0� 02340

Liver

Acute

EA_Pp_67682a

Zgc:77421

�1� 25

0� 02620

Liver

Acute

EA_Pp_70287a

Si:dkey-172o10� 2

�1� 25

0� 03290

Liver

Acute

EA_Pp_66784a

Im:7149790

�1� 26

0� 01280

Liver

Acute

EA_Pp_59653a

Mitogen-activatedprotein

kinase

kinase

kinase

4�1� 26

0� 02100

Liver

Acute

EA_Pp_53037a

Splicingfactor3a,subunit3,60kDa

�1� 27

0� 03490

Liver

Acute

EA_Pp_50585a

Elongationprotein

3homologue

�1� 27

0� 03170

Liver

Acute

EA_Pp_68356a

Chromodomain

helicase

DNA-bindingprotein

1�1� 28

0� 01350

Liver

Acute

EA_Pp_69316a

Pleckstrinhomology-likedomain,familyA,mem

ber

3�1� 28

0� 04710

Liver

Acute

EA_Pp_57894a

Wu:fi37d07

�1� 28

0� 03840


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_70748a

Sim

ilarto

STARTdomain-containing7

�1� 28

0� 00629

Liver

Acute

EA_Pp_69645a

Unknown

�1� 29

0� 03110

Liver

Acute

EA_Pp_62257a

Zgc:91957

�1� 29

0� 04480

Liver

Acute

EA_Pp_62586a

Sim

ilarto

RIK

EN

cDNA

D230014K01

�1� 29

0� 03860

Liver

Acute

EA_Pp_69288a

Amino-terminalenhancerofsplit

�1� 30

0� 03940

Liver

Acute

EA_Pp_61409a

Eukaryotictranslationinitiationfactor2B,subunit1alpha

�1� 30

0� 01970

Liver

Acute

EA_Pp_62224a


54

�1� 31

0� 04270

Liver

Acute

EA_Pp_56448a

Pescadillo

homologue1,containingBRCTdomain

�1� 31

0� 00765

Liver

Acute

EA_Pp_69115a

CCR4-N

OT

transcriptioncomplex,subunit6

�1� 33

0� 01250

Liver

Acute

EA_Pp_58984a

Rhoguaninenucleotideexchangefactor15

�1� 33

0� 03700

Liver

Acute

EA_Pp_60814a

Sec1familydomain-containing2

�1� 34

0� 01140

Liver

Acute

EA_Pp_67536a

TRNA

isopentenyltransferase

1�1� 34

0� 01570

Liver

Acute

EA_Pp_70616a

Hydroxysteroid

11-betadehydrogenase

2�1� 35

0� 00244

Liver

Acute

EA_Pp_57501a

Hypotheticalprotein

HSPC117

�1� 35

0� 02710

Liver

Acute

EA_Pp_63116a

Protein

kinase,interferon-inducible

double-stranded

RNA-dependentinhibitor

�1� 35

0� 01750

Liver

Acute

EA_Pp_58703a

Keratinocyte-associatedprotein

2�1� 35

0� 02600

Liver

Acute

EA_Pp_56995a

Casein

kinase

II,betasubunit

�1� 35

0� 03260

Liver

Acute

EA_Pp_53303a

KCCR13L

�1� 35

0� 04220

Liver

Acute

EA_Pp_65816a

DNA

segment,Chr3,ERATO

Doi194,expressed

�1� 35

0� 04760

Liver

Acute

EA_Pp_59783a

TATA

box-bindingprotein-associatedfactor,RNA

polymerase

I,C,110kDa

�1� 35

0� 01440

Liver

Acute

EA_Pp_62300a

Opioid

receptor,sigma1

�1� 35

0� 01980

Liver

Acute

EA_Pp_53167a

Unknown

�1� 35

0� 02360

Liver

Acute

EA_Pp_61313a

Loss

ofheterozygosity,12,chromosomalregion1homologue

�1� 35

0� 03140

Liver

Acute

EA_Pp_70672a

Eukaryotictranslationinitiationfactor5

�1� 36

0� 04200

Liver

Acute

EA_Pp_59045a

Zgc:56197

�1� 37

0� 01280


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_52935a

Coatomer

protein

complex,subunitbeta2

�1� 37

0� 01460

Liver

Acute

EA_Pp_67994a

Ceroid-lipofuscinosis,neuronal6,late

infantile,variant

�1� 37

0� 02270

Liver

Acute

EA_Pp_62695a

Likelyorthologueofmouse

immediate

earlyresponse,

erythropoietin4

�1� 37

0� 03530

Liver

Acute

EA_Pp_56328a

Exosomecomponent9

�1� 37

0� 04910

Liver

Acute

EA_Pp_64204a

Reticulon3

�1� 37

0� 04500

Liver

Acute

EA_Pp_60355a

Lamin

L3

�1� 38

0� 00786

Liver

Acute

EA_Pp_58743a

Sim

ilarto

dynein,cytoplasm

ic,lightinterm

ediate

chain

1�1� 38

0� 01200

Liver

Acute

EA_Pp_51833a

Stress-induced-phosphoprotein

1�1� 38

0� 04530

Liver

Acute

EA_Pp_69642a

Thioredoxin

reductase

1�1� 39

0� 04970

Liver

Acute

EA_Pp_68269a

Bromodomain

adjacentto

zincfinger

domain,2A

�1� 39

0� 02620

Liver

Acute

EA_Pp_51257a

DEAH

boxpolypeptide35

�1� 39

0� 03440

Liver

Acute

EA_Pp_60829a

IMPdehydrogenase

2�1� 40

0� 02910

Liver

Acute

EA_Pp_57225a

Lamin

L3

�1� 40

0� 01580

Liver

Acute

EA_Pp_51774a

Ubiquitin-conjugatingenzymeE2G

1�1� 40

0� 02080

Liver

Acute

EA_Pp_55596a

Zgc:92863

�1� 40

0� 02670

Liver

Acute

EA_Pp_67393a

Ubiquitin-specificprotease

5�1� 40

0� 04850

Liver

Acute

EA_Pp_59833a

DEAD

boxpolypeptide5

�1� 41

0� 00969

Liver

Acute

EA_Pp_60083a

RIK

EN

cDNA

2900055D14gene

�1� 42

0� 01730

Liver

Acute

EA_Pp_60102a

Zincfinger,HIT

type4

�1� 42

0� 03920

Liver

Acute

EA_Pp_65891a

Unknown

�1� 43

0� 02120

Liver

Acute

EA_Pp_58298a

Polymerase

IIpolypeptideL,7� 6

kDa

�1� 43

0� 00431

Liver

Acute

EA_Pp_53737a

WD

repeatdomain

26

�1� 43

0� 04490

Liver

Acute

EA_Pp_54912a

Zgc:85615

�1� 44

0� 02280

Liver

Acute

EA_Pp_70404a

Pl10

�1� 44

0� 01930

Liver

Acute

EA_Pp_59511a

Sim

ilarto

signaltransducerandactivatoroftranscription1

isoform

beta

�1� 45

0� 01780


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_51989a

Im:7149790

�1� 45

0� 03560

Liver

Acute

EA_Pp_54281a

Nucleolarprotein

family6

�1� 45

0� 01640

Liver

Acute

EA_Pp_58180a

Heterogeneousnuclearribonucleoproteins

methyltransferase-like2

�1� 45

0� 03350

Liver

Acute

EA_Pp_53706a

TBC1domain

family,mem

ber

8�1� 45

0� 02000

Liver

Acute

EA_Pp_62480a

HLA-B-associatedtranscript5

�1� 46

0� 04510

Liver

Acute

EA_Pp_63540a

Motile

sperm

domain-containing2

�1� 46

0� 01440

Liver

Acute

EA_Pp_56588a

Zgc:101724

�1� 46

0� 02690

Liver

Acute

EA_Pp_54925a

Hectdomain

andRLD

2�1� 47

0� 02790

Liver

Acute

EA_Pp_57359a

Unknown

�1� 49

0� 02920

Liver

Acute

EA_Pp_69034a

Cytochrome

b�1� 49

0� 01430

Liver

Acute

EA_Pp_57068a

Swelling-dependentchloridechannel

�1� 49

0� 02060

Liver

Acute

EA_Pp_59116a

Sim

ilarto

metallophosphoesterase

�1� 49

0� 02740

Liver

Acute

EA_Pp_51595a

Ribosomalprotein

L41

�1� 49

0� 04340

Liver

Acute

EA_Pp_61249a

Mitochondrialribosomalprotein

L12

�1� 49

0� 04550

Liver

Acute

EA_Pp_61295a

Familywithsequence

similarity

82,mem

ber

C�1� 50

0� 00470

Liver

Acute

EA_Pp_59825a

TSR1,20SRRNA

accumulation,homologue

�1� 50

0� 02690

Liver

Acute

EA_Pp_51070a

Sim

ilarto

ubiquitin-likeprotein

1�1� 50

0� 01550

Liver

Acute

EA_Pp_50397a

Coatomer

protein

complex,subunitepsilon

�1� 50

0� 03520

Liver

Acute

EA_Pp_68046a


U�1� 51

0� 02160

Liver

Acute

EA_Pp_51562a

Vacuolarprotein

sorting35

�1� 51

0� 03160

Liver

Acute

EA_Pp_59615a

Solute

carrierfamily35,mem

ber

B4

�1� 51

0� 02320

Liver

Acute

EA_Pp_57705a

Transducin-like2

�1� 52

0� 02070

Liver

Acute

EA_Pp_70344a

HLA-B-associatedtranscript1A

�1� 52

0� 03490

Liver

Acute

EA_Pp_52518a

Calbindin-28K

�1� 52

0� 04660

Liver

Acute

EA_Pp_64944a

Nucleolarprotein

familyA,mem

ber

3�1� 52

0� 02640

Liver

Acute

EA_Pp_56429a

RIK

EN

cDNA

9130005N14gene

�1� 53

0� 01630


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_57730a

FOS-likeantigen

1�1� 53

0� 01420

Liver

Acute

EA_Pp_58546a

Ringfinger

andKH

domain-containing3

�1� 53

0� 04710

Liver

Acute

EA_Pp_67092a

RRS1ribosomebiogenesisregulatorhomologue

�1� 54

0� 03120

Liver

Acute

EA_Pp_67225a

RIK

EN

cDNA

B430110G05gene

�1� 54

0� 04400

Liver

Acute

EA_Pp_69857a

Transm

embraneandcoiled-coildomains1

�1� 54

0� 04490

Liver

Acute

EA_Pp_52331a

ATP-bindingcassette,sub-familyE,mem

ber

1�1� 54

0� 04550

Liver

Acute

EA_Pp_52919a

Stearoyl-CoA

desaturase

�1� 54

0� 04700

Liver

Acute

EA_Pp_63832a

Eukaryotictranslationinitiationfactor4A,isoform

1�1� 54

0� 04710

Liver

Acute

EA_Pp_63931a

Hypotheticalprotein

FLJ10808

�1� 55

0� 02400

Liver

Acute

EA_Pp_63356a

Alg5,

Sa

cch

aro

myc

esce

revi

sia

e,homologueof

�1� 55

0� 02770

Liver

Acute

EA_Pp_64736a

Autophagy-related16-like1

�1� 55

0� 01140

Liver

Acute

EA_Pp_54325a

DEAD

boxpolypeptide47

�1� 56

0� 03390

Liver

Acute

EA_Pp_67148a

Guaninenucleotide-bindingprotein-like3

�1� 56

0� 03250

Liver

Acute

EA_Pp_59069a

Zgc:77636

�1� 57

0� 00503

Liver

Acute

EA_Pp_51932a

Protein

tyrosinephosphatase,non-receptortype12

�1� 57

0� 00567

Liver

Acute

EA_Pp_69211a

Surfeit6-like

�1� 57

0� 00700

Liver

Acute

EA_Pp_71031a

Deoxyhypusinesynthase

�1� 57

0� 01220

Liver

Acute

EA_Pp_53172a

Ribosomalprotein

L7-like1

�1� 57

0� 03370

Liver

Acute

EA_Pp_52843a

Cryptochrome2b

�1� 58

0� 00066

Liver

Acute

EA_Pp_52447a

DnaJhomologue,

subfamilyC,mem

ber

10

�1� 59

0� 03310

Liver

Acute

EA_Pp_66337a

Creatinekinase,mitochondrial1

�1� 60

0� 02880

Liver

Acute

EA_Pp_54460a

Sim

ilarto

ADP-ribosylationfactor-like6interactingprotein

2�1� 60

0� 03660

Liver

Acute

EA_Pp_68352a

Down-regulatoroftranscription1,TBP-binding

�1� 61

0� 01530

Liver

Acute

EA_Pp_50643a

Lectin,mannose-binding,1

�1� 61

0� 04920

Liver

Acute

EA_Pp_54717a

COBW

domain-containing1

�1� 61

0� 02010

Liver

Acute

EA_Pp_68987a

Zgc:63626

�1� 62

0� 04590

Liver

Acute

EA_Pp_69475a

ADP-ribosylationfactor2

�1� 62

0� 01230


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_57472a

Sim

ilarto

protein

KIA

A0133

�1� 63

0� 03370

Liver

Acute

EA_Pp_67614a

Serum

response

factor

�1� 63

0� 00197

Liver

Acute

EA_Pp_67816a

Peptidylprolylisomerase-like1

�1� 63

0� 03570

Liver

Acute

EA_Pp_58567a

5-aminoim

idazole-4-carboxamideribonucleotide

form

yltransferase–IM

Pcyclohydrolase

�1� 63

0� 03920

Liver

Acute

EA_Pp_52257a

Sim

ilarto

eukaryotictranslationelongationfactor1epsilon-1

�1� 63

0� 04520

Liver

Acute

EA_Pp_54837a

Zgc:56703

�1� 63

0� 02370

Liver

Acute

EA_Pp_67287a

Transm

embraneprotein

65

�1� 64

0� 01760

Liver

Acute

EA_Pp_60379a

Tripeptidylpeptidase

II�1� 65

0� 02320

Liver

Acute

EA_Pp_58321a

Translocase

ofoutermitochondrialmem

brane70

homologueA

�1� 65

0� 01460

Liver

Acute

EA_Pp_53759a

Riboflavin

kinase

�1� 66

0� 04060

Liver

Acute

EA_Pp_52987a

Surfeit5

�1� 66

0� 00835

Liver

Acute

EA_Pp_56914a

Acyl-CoA

synthetase

long-chain

familymem

ber

4�1� 66

0� 01020

Liver

Acute

EA_Pp_54977a

Unknown

�1� 67

0� 03840

Liver

Acute

EA_Pp_64366a

CDK2-associatedprotein

2�1� 67

0� 04240

Liver

Acute

EA_Pp_51015a

Defender

against

celldeath

1�1� 67

0� 04290

Liver

Acute

EA_Pp_65548a

Mem

braneprotein,palm

itoylated6

�1� 68

0� 02400

Liver

Acute

EA_Pp_54953a

HD

domain-containing2

�1� 68

0� 02890

Liver

Acute

EA_Pp_55374a

Dynein,cytoplasm

ic1lightinterm

ediate

chain

2�1� 68

0� 03790

Liver

Acute

EA_Pp_60479a

Sel11homologue

�1� 69

0� 00819

Liver

Acute

EA_Pp_60786a

Unknown

�1� 69

0� 00982

Liver

Acute

EA_Pp_54181a

Methionine-tR

NA

synthetase

�1� 69

0� 02060

Liver

Acute

EA_Pp_58691a

Zincfinger,MYND

domain-containing19

�1� 70

0� 00533

Liver

Acute

EA_Pp_57194a

Sec61alpha1subunit

�1� 70

0� 02310

Liver

Acute

EA_Pp_60613a


�1� 71

0� 03040

Liver

Acute

EA_Pp_57536a

RadandGem

-relatedGTP-bindingprotein

1�1� 71

0� 04670


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_52130a

Splicingfactor3b,subunit4

�1� 71

0� 04750

Liver

Acute

EA_Pp_57802a

Dihydrouridinesynthase

1-like

�1� 72

0� 01280

Liver

Acute

EA_Pp_51391a

UDP-N

-acetyl-alpha-D

-galactosamine:

polypeptide

N-acetylgalactosaminyltransferase

12

�1� 72

0� 00869

Liver

Acute

EA_Pp_68412a

Solute

carrierfamily38,mem

ber

3�1� 72

0� 01870

Liver

Acute

EA_Pp_68899a

RIK

EN

cDNA

2310008M10gene

�1� 73

0� 02180

Liver

Acute

EA_Pp_61290a

WD

repeatdomain

36

�1� 73

0� 02830

Liver

Acute

EA_Pp_50370a

AFG3ATPase

familygene3-like2

�1� 73

0� 03330

Liver

Acute

EA_Pp_54121a

Kinectin1

�1� 73

0� 04090

Liver

Acute

EA_Pp_63887a

Protein

disulfideisomerase

familyA,mem

ber

3�1� 74

0� 02520

Liver

Acute

EA_Pp_54206a

MGC79752protein

�1� 74

0� 02780

Liver

Acute

EA_Pp_66495a

PutativeATP-dependentRNA

helicase

�1� 74

0� 04430

Liver

Acute

EA_Pp_66840a

Zgc:92026

�1� 75

0� 03060

Liver

Acute

EA_Pp_55102a

Polymerase-I-associatedfactor1

�1� 76

0� 01580

Liver

Acute

EA_Pp_62175a

RIK

EN

cDNA

5730537D05gene

�1� 76

0� 02460

Liver

Acute

EA_Pp_57973a

Sim

ilarto

CG8414-PA

�1� 77

0� 04910

Liver

Acute

EA_Pp_61252a

Zgc:77767

�1� 77

0� 01650

Liver

Acute

EA_Pp_57630a

Cyclin-dependentkinase

8�1� 78

0� 02900

Liver

Acute

EA_Pp_66730a

BRF1homologue,

subunitofRNA

polymerase

III

transcriptioninitiationfactorIIIB

�1� 79

0� 00556

Liver

Acute

EA_Pp_66702a

Unknown

�1� 80

0� 03540

Liver

Acute

EA_Pp_54099a

MitochondrialCOX18

�1� 80

0� 04490

Liver

Acute

EA_Pp_58806a

Zgc:56141

�1� 80

0� 00495

Liver

Acute

EA_Pp_53523a

Zgc:76871

�1� 80

0� 02000

Liver

Acute

EA_Pp_60606a

Beta-catenin-interactingprotein

�1� 81

0� 01520

Liver

Acute

EA_Pp_70545a

Chromosome1open

readingframe33

�1� 81

0� 00987

Liver

Acute

EA_Pp_57001a

Mesoderm

developmentcandidate

2�1� 81

0� 04280


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_57455a

Importin

4�1� 82

0� 03500

Liver

Acute

EA_Pp_56920a

ATP-bindingcassette,subfamilyF,mem

ber

3�1� 82

0� 03570

Liver

Acute

EA_Pp_56197a

Zgc:63842

�1� 82

0� 02410

Liver

Acute

EA_Pp_70635a

Unknown

�1� 82

0� 03100

Liver

Acute

EA_Pp_56540a

Proteasomeactivatorsubunit3

�1� 83

0� 02420

Liver

Acute

EA_Pp_59369a

CytochromeP450,family4,subfamilyV,polypeptide2

�1� 84

0� 02960

Liver

Acute

EA_Pp_50168a

Serinedehydratase

�1� 84

0� 00770

Liver

Acute

EA_Pp_59334a

Nucleolarprotein

5�1� 86

0� 03070

Liver

Acute

EA_Pp_59245a

Zgc:92026

�1� 86

0� 03110

Liver

Acute

EA_Pp_65894a

Unknown

�1� 86

0� 00305

Liver

Acute

EA_Pp_63059a

Oxidativestress

responsive1

�1� 86

0� 00949

Liver

Acute

EA_Pp_60477a

Unknown

�1� 86

0� 02330

Liver

Acute

EA_Pp_65383a


14

�1� 87

0� 02510

Liver

Acute

EA_Pp_66908a

Eukaryotictranslationinitiationfactor1A,X-linked

�1� 88

0� 03640

Liver

Acute

EA_Pp_56175a

UDP-glucose

ceramideglucosyltransferase-like1

�1� 88

0� 03830

Liver

Acute

EA_Pp_50462a

MGC82689protein

�1� 89

0� 02570

Liver

Acute

EA_Pp_69193a

Mitochondrialtopoisomerase

I�1� 89

0� 04400

Liver

Acute

EA_Pp_59517a

Zgc:64095

�1� 90

0� 00403

Liver

Acute

EA_Pp_50484a

Cysteine-rich

withEGF-likedomains2

�1� 91

0� 03630

Liver

Acute

EA_Pp_60592a

Nucleolarprotein

familyA,mem

ber

1�1� 91

0� 00912

Liver

Acute

EA_Pp_63593a

Leucyl-tR

NA

synthetase

�1� 92

0� 02240

Liver

Acute

EA_Pp_68852a

Zgc:85671

�1� 93

0� 04010

Liver

Acute

EA_Pp_55202a

Thioesterase

domain-containing1

�1� 94

0� 02790

Liver

Acute

EA_Pp_57567a

Nucleoporin50

�1� 95

0� 02160

Liver

Acute

EA_Pp_57368a

Ubiquitin-like1-activatingenzymeE1A

�1� 95

0� 02500

Liver

Acute

EA_Pp_54251a

Acyl-CoA

synthetase

long-chain

familymem

ber

3�1� 95

0� 04400

Liver

Acute

EA_Pp_55957a

Zgc:92008

�1� 96

0� 01690


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_56191a

Solute

carrierfamily39,mem

ber

9�1� 96

0� 04230

Liver

Acute

EA_Pp_56982a

Protein

kinase

inhibitorbeta,CAMPdependent,testisspecific

�1� 97

0� 01570

Liver

Acute

EA_Pp_68593a

MGC83844protein

�1� 97

0� 00832

Liver

Acute

EA_Pp_50339a

D121protein

�1� 98

0� 01780

Liver

Acute

EA_Pp_51986a

WD

repeatdomain

12

�1� 99

0� 00480

Liver

Acute

EA_Pp_66621a

Dolichyl-di-phosphooligosaccharide-protein

glycotransferase

�1� 99

0� 02260

Liver

Acute

EA_Pp_69363a

Nucleolarprotein

11

�1� 99

0� 04950

Liver

Acute

EA_Pp_57962a

Unknown

�2� 00

0� 02770

Liver

Acute

EA_Pp_62230a

Zgc:86704

�2� 00

0� 03000

Liver

Acute

EA_Pp_60347a

Nucleophosm

in1

�2� 01

0� 02890

Liver

Acute

EA_Pp_64395a

Sim

ilarto

KIA

A1822protein

�2� 02

0� 04810

Liver

Acute

EA_Pp_56320a


�2� 02

0� 04600

Liver

Acute

EA_Pp_50847a

Fibrillarin

�2� 03

0� 02430

Liver

Acute

EA_Pp_50111a

Unknown

�2� 04

0� 02580

Liver

Acute

EA_Pp_58874a

Solute

carrierfamily6,mem

ber

13

�2� 05

0� 02290

Liver

Acute

EA_Pp_64005a

Zgc:56457

�2� 06

0� 01580

Liver

Acute

EA_Pp_69226a

CDC37celldivisioncycle37homologue

�2� 08

0� 02480

Liver

Acute

EA_Pp_61307a

Sim

ilarto

zincfinger

protein

262

�2� 09

0� 01010

Liver

Acute

EA_Pp_57649a

Cysteineconjugate-betalyase

2�2� 09

0� 04810

Liver

Acute

EA_Pp_67397a

Polymerase

IIpolypeptideH

�2� 10

0� 01420

Liver

Acute

EA_Pp_53797a

Zgc:85939

�2� 10

0� 01540

Liver

Acute

EA_Pp_53999a

Zgc:63943

�2� 10

0� 03660

Liver

Acute

EA_Pp_69551a

Smallfragmentnuclease

�2� 14

0� 04840

Liver

Acute

EA_Pp_51659a

Zgc:65780

�2� 15

0� 01930

Liver

Acute

EA_Pp_63985a

Zgc:92136

�2� 15

0� 02880

Liver

Acute

EA_Pp_50503a

Asparagine-linked

glycosylation9homologue

�2� 16

0� 02200

Liver

Acute

EA_Pp_70840a

Glutamate-cysteineligase,modifier

subunit

�2� 16

0� 04150


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_61475a

Hypotheticalprotein

MGC68732

�2� 18

0� 00773

Liver

Acute

EA_Pp_55565a


14kDa

�2� 18

0� 04690

Liver

Acute

EA_Pp_60925a

Chromosome20open

readingframe149homologue

�2� 20

0� 01990

Liver

Acute

EA_Pp_57816a

Zgc:92628

�2� 21

0� 00438

Liver

Acute

EA_Pp_68618a

Zgc:56174

�2� 21

0� 01490

Liver

Acute

EA_Pp_68139a

Unknown

�2� 21

0� 01900

Liver

Acute

EA_Pp_55506a

High-m

obilitygroupbox3

�2� 22

0� 01880

Liver

Acute

EA_Pp_60191a

TarRNA-bindingprotein

1�2� 22

0� 03060

Liver

Acute

EA_Pp_63431a

Hydroxymethylbilanesynthase

�2� 23

0� 00853

Liver

Acute

EA_Pp_62052a

Zgc:56668

�2� 24

0� 01280

Liver

Acute

EA_Pp_67216a


�2� 24

0� 03250

Liver

Acute

EA_Pp_70328a

Zincfinger

andBTBdomain-containing16

�2� 25

0� 02830

Liver

Acute

EA_Pp_50563a

Transm

embrane,

prostate

androgen-inducedRNA

�2� 25

0� 04750

Liver

Acute

EA_Pp_56912a

Neuraladhesionmolecule

L1� 2

�2� 26

0� 00436

Liver

Acute

EA_Pp_54369a

Polymerase

IIIpolypeptideH

�2� 27

0� 03120

Liver

Acute

EA_Pp_61166a

Pitrilysinmetalloproteinase

1�2� 28

0� 04910

Liver

Acute

EA_Pp_55334a

Protein

disulfideisomerase-associated4

�2� 31

0� 02250

Liver

Acute

EA_Pp_52056a

ATPase

type13A1

�2� 31

0� 03160

Liver

Acute

EA_Pp_52128a

RER1retentionin

endoplasm

icreticulum

1homologue

�2� 32

0� 04450

Liver

Acute

EA_Pp_60207a

Zgc:64182

�2� 37

0� 01380

Liver

Acute

EA_Pp_64320a

Proteasome26Ssubunit,non-A

TPase,8

�2� 39

0� 04420

Liver

Acute

EA_Pp_60591a

Zgc:77751

�2� 39

0� 04800

Liver

Acute

EA_Pp_55187a

Minichromosomemaintenance

deficient6

�2� 43

0� 04360

Liver

Acute

EA_Pp_52395a

Zgc:63563

�2� 44

0� 03610

Liver

Acute

EA_Pp_54543a

Unknown

�2� 50

0� 03230

Liver

Acute

EA_Pp_66560a

ATPase

family,AAA

domain-containing3A

�2� 55

0� 03410

Liver

Acute

EA_Pp_54472a

Arginyl-tR

NA

synthetase

�2� 59

0� 02580


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_57451a

5-m

ethyltetrahydrofolate-homocysteinemethyltransferase

�2� 60

0� 04530

Liver

Acute

EA_Pp_61963a

Fattyacid-bindingprotein

3,muscle

andheart

�2� 61

0� 04920

Liver

Acute

EA_Pp_65522a

Heatshock

60kDaprotein

1�2� 62

0� 01360

Liver

Acute

EA_Pp_54884a

Zgc:77476

�2� 62

0� 03710

Liver

Acute

EA_Pp_60019a

Roundabouthomologue1

�2� 63

0� 04540

Liver

Acute

EA_Pp_58493a

Arginine-rich,mutatedin

early-stagetumours

�2� 64

0� 00933

Liver

Acute

EA_Pp_59081a

Zgc:101717

�2� 77

0� 04920

Liver

Acute

EA_Pp_55747a

Sim

ilarto

protein

I-147

�2� 81

0� 03300

Liver

Acute

EA_Pp_50072a

Sim

ilarto

putativecytoplasm

icprotein

familymem

ber

ofancientorigin

�2� 84

0� 01680

Liver

Acute

EA_Pp_66944a

Pelota

homologue

�2� 88

0� 04960

Liver

Acute

EA_Pp_62029a

Unknown

�2� 94

0� 04500

Liver

Acute

EA_Pp_62107a

Hypoxia

upregulated1

�2� 95

0� 01730

Liver

Acute

EA_Pp_62051a

Zgc:73225

�2� 98

0� 04190

Liver

Acute

EA_Pp_66687a

Translocatingchain-associatingmem

braneprotein

�3� 04

0� 03940

Liver

Acute

EA_Pp_56523a

Galactose-4-epim

erase,UDP

�3� 07

0� 01770

Liver

Acute

EA_Pp_65766a

Hypoxia

upregulated1

�3� 10

0� 02280

Liver

Acute

EA_Pp_53262a

Fattyacidsynthase

�3� 10

0� 04440

Liver

Acute

EA_Pp_55159a

Calcium–calm

odulin-dependentprotein

kinase

ID�3� 17

0� 00696

Liver

Acute

EA_Pp_63319a

Sim

ilarto

RIK

EN

cDNA

2210417D09

�3� 17

0� 00696

Liver

Acute

EA_Pp_65665a

NADH

dehydrogenase

1alphasubcomplex,6

�3� 31

0� 03640

Liver

Acute

EA_Pp_57434a

Heatshock

70kDaprotein

5�3� 38

0� 02800

Liver

Acute

EA_Pp_52975a

Sim

ilarto

DEAH

boxpolypeptide30isoform

2�3� 44

0� 03190

Liver

Acute

EA_Pp_50496a

Unknown

�3� 51

0� 03600

Liver

Acute

EA_Pp_56944a

Retinoldehydrogenase

14

�3� 67

0� 04440

Liver

Acute

EA_Pp_60969a

Calcium-andintegrin-bindingfamilymem

ber

2�3� 69

0� 04190

Liver

Acute

EA_Pp_70325a

Hypotheticalprotein

LOC407708

�4� 67

0� 02110


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Acute

EA_Pp_60220a

MHC

class

IUBA

gene

�9� 40

0� 00035

Liver

Chronic

EA_Pp_68944a

GLE1RNA

export

mediator-like

3� 61

0� 02450

Liver

Chronic

EA_Pp_54098a

Zgc:101806

3� 59

0� 01020

Liver

Chronic

EA_Pp_67443a

Plasm

inogen

activator,tissue

3� 55

0� 00069

Liver

Chronic

EA_Pp_69710a

Phosphomannomutase

13� 07

0� 00859

Liver

Chronic

EA_Pp_58323a

Kinase

suppressorofRas1

2� 69

0� 01990

Liver

Chronic

EA_Pp_56561a

Zgc:100907

2� 66

0� 01810

Liver

Chronic

EA_Pp_56512a

Sim

ilarto

DOCK180-relatedCdc42guanine

nucleotideexchangefactor

2� 64

0� 02540

Liver

Chronic

EA_Pp_64771a

Poly

polymerase

family,mem

ber

82� 32

0� 00640

Liver

Chronic

EA_Pp_66486a

Hypotheticalprotein

LOC571020

2� 28

0� 03020

Liver

Chronic

EA_Pp_54364a

Zgc:92720

2� 27

0� 02280

Liver

Chronic

EA_Pp_50910a

Sim

ilarto

MGC81165protein

2� 20

0� 01940

Liver

Chronic

EA_Pp_70223a

Hypotheticalprotein

LOC567624

2� 18

0� 04120

Liver

Chronic

EA_Pp_56149a

Periodhomologue4

2� 16

0� 01330

Liver

Chronic

EA_Pp_51662a

Hypotheticalprotein

FLJ35630

2� 11

0� 04150

Liver

Chronic

EA_Pp_54672a

Sim

ilarto

DNA

mismatchrepairprotein

Mlh3

2� 02

0� 00973

Liver

Chronic

EA_Pp_64482a

Death

effectordomain-containing1

2� 02

0� 04410

Liver

Chronic

EA_Pp_52153a

DNA

cross-linkrepair1A

2� 01

0� 04840

Liver

Chronic

EA_Pp_63882a

Zgc:55813

1� 99

0� 01110

Liver

Chronic

EA_Pp_68845a

Hypotheticalprotein

LOC562347

1� 94

0� 03420

Liver

Chronic

EA_Pp_55283a

Hypotheticalprotein

FLJ23322

1� 90

0� 01360

Liver

Chronic

EA_Pp_67060a

Tax1-bindingprotein

11� 86

0� 01670

Liver

Chronic

EA_Pp_57545a

Outerdense

fibre

ofsperm

tails2

1� 86

0� 00783

Liver

Chronic

EA_Pp_58163a

Zgc:92851

1� 84

0� 03930

Liver

Chronic

EA_Pp_54190a

Zincfinger

protein

160

1� 83

0� 02030

Liver

Chronic

EA_Pp_67871a

Zgc:66482

1� 82

0� 02200


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Chronic

EA_Pp_51872a

Kruppel-likefactor13

1� 80

0� 04930

Liver

Chronic

EA_Pp_58155a

Procollagen,typeXV

1� 79

0� 04330

Liver

Chronic

EA_Pp_51933a

Caspase

61� 78

0� 03020

Liver

Chronic

EA_Pp_51063a

Sim

ilarto

N-acetylglucosamine-1-phosphodiester

Alpha-N

-acetylglucosaminidase

precursor

1� 77

0� 02340

Liver

Chronic

EA_Pp_62192a

CG33248-PA

1� 70

0� 03040

Liver

Chronic

EA_Pp_55376a

RIK

EN

cDNA

1110018J18gene

1� 69

0� 01120

Liver

Chronic

EA_Pp_50209a

Expressed

sequence

AA536717

1� 66

0� 00759

Liver

Chronic

EA_Pp_54698a

tRNA


34homologue

1� 64

0� 00812

Liver

Chronic

EA_Pp_55675a

Lysosomaltraffickingregulator

1� 63

0� 02630

Liver

Chronic

EA_Pp_70915a

Solute

carrierfamily22,mem

ber

17

1� 62

0� 00849

Liver

Chronic

EA_Pp_58919a

RAB40B,mem

ber

RASoncogenefamily

1� 62

0� 01300

Liver

Chronic

EA_Pp_66230a

Myeloid

cellleukaem

iasequence

1b

1� 60

0� 04900

Liver

Chronic

EA_Pp_65708a

Chromosome1open

readingframe159

1� 58

0� 04850

Liver

Chronic

EA_Pp_53859a

Chromosome1open

readingframe176

1� 57

0� 03260

Liver

Chronic

EA_Pp_50582a

Unc-13homologueB

1� 55

0� 03720

Liver

Chronic

EA_Pp_65193a

AnkyrinrepeatandBTBdomain-containing1

1� 53

0� 00440

Liver

Chronic

EA_Pp_67099a

Myocilin

1� 51

0� 02320

Liver

Chronic

EA_Pp_55426a

Hypotheticalprotein

LOC553231

1� 51

0� 01410

Liver

Chronic

EA_Pp_67717a

PHD

finger

protein

21A

1� 50

0� 02530

Liver

Chronic

EA_Pp_69653a

Zgc:101584

1� 49

0� 00831

Liver

Chronic

EA_Pp_54205a

Heatshock

factor2

1� 43

0� 00255

Liver

Chronic

EA_Pp_65679a

RIK

EN

cDNA

5830411E10gene

1� 42

0� 03680

Liver

Chronic

EA_Pp_65984a

Sim

ilarto

solute

carrierfamily38,mem

ber

21� 41

0� 03060

Liver

Chronic

EA_Pp_63286a

Zgc:92551

1� 40

0� 04390

Liver

Chronic

EA_Pp_68665a

Hypotheticalprotein

LOC562239

1� 39

0� 00032

Liver

Chronic

EA_Pp_63866a

Galactosidase,alpha

1� 38

0� 00312


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Chronic

EA_Pp_67898a

Sim

ilarto

zincfinger

protein

551

1� 36

0� 02630

Liver

Chronic

EA_Pp_62998a

Sim

ilarto

MGC89374protein

1� 35

0� 03650

Liver

Chronic

EA_Pp_61095a

Glypican5

1� 35

0� 02680

Liver

Chronic

EA_Pp_59422a

Hypotheticalprotein

LOC402864

1� 35

0� 01720

Liver

Chronic

EA_Pp_55972a

Short

coiled-coilprotein

1� 35

0� 02520

Liver

Chronic

EA_Pp_54859a

Unknown

1� 34

0� 00631

Liver

Chronic

EA_Pp_57096a

Sim

ilarto

remodellingandspacingfactor1

1� 33

0� 01480

Liver

Chronic

EA_Pp_53730a

CytochromeP450,family39,subfamilyA,polypeptide1

1� 32

0� 03500

Liver

Chronic

EA_Pp_56483a

Phosphatidylcholinetransfer

protein

1� 31

0� 03770

Liver

Chronic

EA_Pp_66247a

Potassium

channel

tetramerisationdomain-containing9

1� 31

0� 04640

Liver

Chronic

EA_Pp_62038a

Hypotheticalprotein

LOC563676

1� 31

0� 02280

Liver

Chronic

EA_Pp_61320a

Exocyst

complexcomponent5

1� 30

0� 01180

Liver

Chronic

EA_Pp_67663a

Hypotheticalprotein

LOC553468

1� 29

0� 03090

Liver

Chronic

EA_Pp_56283a

Vesicle-associatedmem

braneprotein

81� 27

0� 04130

Liver

Chronic

EA_Pp_59865a

WD

repeatdomain

48

1� 26

0� 01620

Liver

Chronic

EA_Pp_65267a

PAP-associateddomain-containing4

1� 26

0� 01300

Liver

Chronic

EA_Pp_50082a

Brutonagammaglobulinaem

iatyrosinekinase

1� 24

0� 00964

Liver

Chronic

EA_Pp_64487a

Jumonjidomain-containing2A

like

1� 23

0� 00915

Liver

Chronic

EA_Pp_67518a

Hypotheticalprotein

LOC569147

1� 22

0� 04620

Liver

Chronic

EA_Pp_63824a

Sim

ilarto

zincfinger

protein

84

1� 21

0� 04330

Liver

Chronic

EA_Pp_60743a

CDC-likekinase

11� 21

0� 01980

Liver

Chronic

EA_Pp_54192a

Sim

ilarto

tetraspanNET-7

1� 19

0� 00918

Liver

Chronic

EA_Pp_69799a

Cappuccinohomologue

1� 17

0� 00388

Liver

Chronic

EA_Pp_56718a

Caspase


1� 16

0� 02030

Liver

Chronic

EA_Pp_67651a

Zgc:123015

1� 15

0� 04300

Liver

Chronic

EA_Pp_58299a

Zgc:63666

1� 14

0� 02440

Liver

Chronic

EA_Pp_54924a

Protein

phosphatase

1,regulatory

subunit15A

1� 14

0� 02760


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Chronic

EA_Pp_67498a

Adaptor-relatedprotein

complex4,beta-1

subunit-like

1� 13

0� 03640

Liver

Chronic

EA_Pp_56871a

TAR

DNA-bindingprotein

1� 13

0� 01810

Liver

Chronic

EA_Pp_51032a

Hypotheticalprotein

FLJ20294

1� 12

0� 04550

Liver

Chronic

EA_Pp_61076a

Solute

carrierfamily35,mem

ber

A5

1� 12

0� 02120

Liver

Chronic

EA_Pp_68505a

Sim

ilarto

butyrophilin

31� 11

0� 01500

Liver

Chronic

EA_Pp_56738a

DnaJhomologue,

subfamilyB,mem

ber

61� 11

0� 00397

Liver

Chronic

EA_Pp_57454a

Transientreceptorpotentialcationchannel,subfamilyM,

mem

ber

71� 10

0� 03740

Liver

Chronic

EA_Pp_50093a

Sim

ilarto

RIK

EN

cDNA

2610318G18

1� 10

0� 04180

Liver

Chronic

EA_Pp_55626a

Sim

ilarto

coiled-coildomain-containing14

1� 09

0� 02880

Liver

Chronic

EA_Pp_52033a

Heparansulphate

3-O

-sulfotransferase

11� 07

0� 02720

Liver

Chronic

EA_Pp_51533a

Zgc:92283

1� 07

0� 01130

Liver

Chronic

EA_Pp_64099a

F-boxandleucine-rich

repeatprotein

61� 06

0� 03730

Liver

Chronic

EA_Pp_62727a

XK,Kellbloodgroupcomplexsubunit-relatedfamily,

mem

ber

81� 04

0� 01830

Liver

Chronic

EA_Pp_54836a

Sim

ilarto

splicingfactor,arginine/serine-rich

41� 04

0� 02380

Liver

Chronic

EA_Pp_58249a

Integratorcomplexsubunit4

1� 03

0� 04820

Liver

Chronic

EA_Pp_66211a

Deform

edepidermalautoregulatory

factor1

1� 03

0� 03270

Liver

Chronic

EA_Pp_56424a

PQ-looprepeat-containing2

1� 03

0� 02430

Liver

Chronic

EA_Pp_56326a

RIK

EN

cDNA

2610304F09gene

1� 02

0� 00440

Liver

Chronic

EA_Pp_57653a

NADPH-dependentdiflavin

oxidoreductase

11� 00

0� 00073

Liver

Chronic

EA_Pp_52099a

RNA-bindingmotifprotein

18

1� 00

0� 00639

Liver

Chronic

EA_Pp_51646a

Unknown

�1� 00

0� 04480

Liver

Chronic

EA_Pp_59449a

RASprotein

activatorlike1

�1� 01

0� 00975

Liver

Chronic

EA_Pp_57719a

Vestigiallike4

�1� 01

0� 03430

Liver

Chronic

EA_Pp_60962a

Zincfinger,RAN-bindingdomain-containing1

�1� 01

0� 04480

Liver

Chronic

EA_Pp_68437a

Ankyrin3,epithelial

�1� 02

0� 00423


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Chronic

EA_Pp_56310a

Chromosome21open

readingframe18

�1� 02

0� 03680

Liver

Chronic

EA_Pp_69207a

CytochromeP450,family2,subfamilyF,polypeptide1

�1� 02

0� 00023

Liver

Chronic

EA_Pp_70527a

RIK

EN

cDNA

9130023D20gene

�1� 02

0� 03570

Liver

Chronic

EA_Pp_54436a

Zgc:55954

�1� 02

0� 04750

Liver

Chronic

EA_Pp_52791a

Chromosome1open

readingframe9

�1� 03

0� 03430

Liver

Chronic

EA_Pp_55165a

ADP-ribosylationfactorguaninenucleotideexchangefactor2

�1� 04

0� 03400

Liver

Chronic

EA_Pp_53637a

Ataxin

1�1� 04

0� 01330

Liver

Chronic

EA_Pp_61832a

Junctophilin

1�1� 05

0� 02640

Liver

Chronic

EA_Pp_53318a

Translocase

ofinner

mitochondrialmem

brane44

�1� 05

0� 03090

Liver

Chronic

EA_Pp_60448a

Unknown

�1� 06

0� 00802

Liver

Chronic

EA_Pp_61492a

Zgc:77038

�1� 06

0� 04000

Liver

Chronic

EA_Pp_56119a

Unknown

�1� 07

0� 00578

Liver

Chronic

EA_Pp_52569a

cDNA

sequence

BC030863

�1� 07

0� 04810

Liver

Chronic

EA_Pp_68560a

Microtubule-associatedprotein

Tau

�1� 07

0� 02440

Liver

Chronic

EA_Pp_59802a

WD

repeatdomain

75

�1� 07

0� 04550

Liver

Chronic

EA_Pp_51767a


kinase

10

�1� 07

0� 04590

Liver

Chronic

EA_Pp_50256a

Unknown

�1� 07

0� 04840

Liver

Chronic

EA_Pp_52931a

Unknown

�1� 08

0� 04320

Liver

Chronic

EA_Pp_50881a

ElongationfactorTuGTP-bindingdomain-containing2

�1� 08

0� 04870

Liver

Chronic

EA_Pp_67647a

MGC81803protein

�1� 08

0� 00896

Liver

Chronic

EA_Pp_70878a

Unknown

�1� 08

0� 01800

Liver

Chronic

EA_Pp_69468a

G-protein-coupledreceptor85

�1� 08

0� 02290

Liver

Chronic

EA_Pp_63395a

Hypotheticalprotein

FLJ13089

�1� 08

0� 02660

Liver

Chronic

EA_Pp_67282a

Potassium

inwardly-rectifyingchannel,subfamilyJ,mem

ber

3�1� 09

0� 03420

Liver

Chronic

EA_Pp_63543a

Synaptotagmin

XV

�1� 10

0� 00851

Liver

Chronic

EA_Pp_57870a

Unknown

�1� 10

0� 02770

Liver

Chronic

EA_Pp_56749a

Sim

ilarto

novel

homeodomain

protein

�1� 10

0� 01030


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Chronic

EA_Pp_59779a

KIA

A1466gene

�1� 10

0� 03090

Liver

Chronic

EA_Pp_63778a

Unknown

�1� 11

0� 03060

Liver

Chronic

EA_Pp_54015a

Unknown

�1� 11

0� 03540

Liver

Chronic

EA_Pp_62616a

Sim

ilarto

radiation-inducible

immediate

earlygeneIE

X-1

�1� 11

0� 01060

Liver

Chronic

EA_Pp_66032a

Sim

ilarto

CG3184-PA

�1� 12

0� 00316

Liver

Chronic

EA_Pp_58449a

Unknown

�1� 12

0� 04030

Liver

Chronic

EA_Pp_58654a

Unknown

�1� 13

0� 01340

Liver

Chronic

EA_Pp_65959a

Synaptotagmin

binding,cytoplasm

icRNA-interactingprotein

�1� 13

0� 02780

Liver

Chronic

EA_Pp_66581a

Sim

ilarto

catenin,delta

1�1� 13

0� 03040

Liver

Chronic

EA_Pp_59658a

Synaptotagmin

6�1� 13

0� 04550

Liver

Chronic

EA_Pp_57684a

Chromosome1open

readingframe60

�1� 13

0� 04770

Liver

Chronic

EA_Pp_54216a

Cyclin

D1

�1� 14

0� 04060

Liver

Chronic

EA_Pp_59334a

Nucleolarprotein

5�1� 14

0� 03480

Liver

Chronic

EA_Pp_70134a

Protein

disulfideisomerase

familyA,mem

ber

3�1� 14

0� 01900

Liver

Chronic

EA_Pp_66495a

EmbryonalFyn-associatedsubstrate

�1� 14

0� 03700

Liver

Chronic

EA_Pp_56329a

Vang-like1

�1� 15

0� 04500

Liver

Chronic

EA_Pp_54125a

Notchgenehomologue1

�1� 16

0� 01750

Liver

Chronic

EA_Pp_52456a

Translocase

ofinner

mitochondrialmem

brane23homologue

�1� 17

0� 04730

Liver

Chronic

EA_Pp_53639a


1homologue180kDa

�1� 18

0� 02810

Liver

Chronic

EA_Pp_65246a

Islet3

�1� 18

0� 01760

Liver

Chronic

EA_Pp_56697a

Abhydrolase

domain-containing10

�1� 19

0� 04880

Liver

Chronic

EA_Pp_55055a

MGC80698protein

�1� 19

0� 04040

Liver

Chronic

EA_Pp_56674a

Aldehydeoxidase

1�1� 20

0� 01660

Liver

Chronic

EA_Pp_60698a

Dynamin

2�1� 20

0� 00670

Liver

Chronic

EA_Pp_66252a

Furin

�1� 20

0� 00947

Liver

Chronic

EA_Pp_67074a

Eukaryotictranslationinitiationfactor4gamma,3

�1� 20

0� 01070

Liver

Chronic

EA_Pp_67680a

Protein

phosphatase

2,regulatory

subunitB,gammaisoform

�1� 22

0� 01760


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Chronic

EA_Pp_70917a

Zgc:109983

�1� 22

0� 04870

Liver

Chronic

EA_Pp_57348a

WD

repeatdomain

3�1� 22

0� 01590

Liver

Chronic

EA_Pp_56703a

Transketolase

�1� 23

0� 00726

Liver

Chronic

EA_Pp_52475a

Zgc:66359

�1� 23

0� 00977

Liver

Chronic

EA_Pp_57271a

Sim

ilarto

mem

braneprotein

MKirre

�1� 24

0� 04760

Liver

Chronic

EA_Pp_57130a

Unknown

�1� 24

0� 02670

Liver

Chronic

EA_Pp_50248a

Chromosome10open

readingframe38

�1� 25

0� 02490

Liver

Chronic

EA_Pp_60472a

Tumourprotein

p53-bindingprotein

1�1� 26

0� 00356

Liver

Chronic

EA_Pp_70193a

Hookhomologue3

�1� 27

0� 03120

Liver

Chronic

EA_Pp_68629a

Nuclearubiquitouscasein

andcyclin-dependentkinase

substrate

�1� 27

0� 02730

Liver

Chronic

EA_Pp_52157a

CCAAT–enhancer-bindingprotein,alpha

�1� 27

0� 02970

Liver

Chronic

EA_Pp_53999a

Zgc:85939

�1� 28

0� 04820

Liver

Chronic

EA_Pp_54562a

Metaxin

2�1� 28

0� 01470

Liver

Chronic

EA_Pp_56939a

Unknown

�1� 29

0� 01140

Liver

Chronic

EA_Pp_58872a

Hypotheticalprotein

LOC555871

�1� 29

0� 02360

Liver

Chronic

EA_Pp_58287a

Transaldolase

1�1� 29

0� 03390

Liver

Chronic

EA_Pp_56478a

Glutathionereductase

1�1� 30

0� 01130

Liver

Chronic

EA_Pp_65798a

Zincfinger

protein

36,C3H

type-like1

�1� 30

0� 03840

Liver

Chronic

EA_Pp_50535a

Unknown

�1� 30

0� 04690

Liver

Chronic

EA_Pp_50982a

Complementcomponent1,Q

subcomponent,

betapolypeptide

�1� 30

0� 01760

Liver

Chronic

EA_Pp_50234a

Im:7151472

�1� 31

0� 01460

Liver

Chronic

EA_Pp_52344a

Chromodomain

helicase

DNA-bindingprotein

7�1� 33

0� 01230

Liver

Chronic

EA_Pp_55262a

Polymerase

IIpolypeptideJ,

13� 3

kDa

�1� 33

0� 03900

Liver

Chronic

EA_Pp_69626a

Nicotinamidenucleotideadenylyltransferase

2�1� 33

0� 04260

Liver

Chronic

EA_Pp_61041a

Sim

ilarto

MGC86473protein

�1� 35

0� 02940


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Chronic

EA_Pp_59924a

CREB-bindingprotein

�1� 36

0� 00897

Liver

Chronic

EA_Pp_51901a

Unknown

�1� 36

0� 02280

Liver

Chronic

EA_Pp_56971a

Histidineacidphosphatase

domain-containing1

�1� 36

0� 04380

Liver

Chronic

EA_Pp_53416a

Zgc:92668

�1� 37

0� 01380

Liver

Chronic

EA_Pp_65174a

Sim

ilarto

protein

KIA

A0133

�1� 37

0� 03220

Liver

Chronic

EA_Pp_57472a

Synaptotagmin-like1

�1� 37

0� 04230

Liver

Chronic

EA_Pp_62563a

SRY-box-containinggene11

�1� 38

0� 03330

Liver

Chronic

EA_Pp_64862a

FCH

domain

only

2�1� 38

0� 03450

Liver

Chronic

EA_Pp_60443a

CD200antigen

�1� 38

0� 03870

Liver

Chronic

EA_Pp_62186a

Sim

ilarto

1-phosphatidylinositol-4,5-bisphosphate

phosphodiesterase

gamma2

�1� 39

0� 01690

Liver

Chronic

EA_Pp_55307a

Zgc:56065

�1� 40

0� 01840

Liver

Chronic

EA_Pp_57423a

RIK

EN

cDNA

2810417M05gene

�1� 41

0� 00355

Liver

Chronic

EA_Pp_57059a

Glycosyltransferase

25domain-containing1

�1� 41

0� 01920

Liver

Chronic

EA_Pp_70607a

cDNA

sequence

BC022641

�1� 44

0� 02340

Liver

Chronic

EA_Pp_66562a

Proline,

glutamic

acidandleucine-rich

protein

1�1� 44

0� 04680

Liver

Chronic

EA_Pp_50937a

Zgc:92810

�1� 46

0� 03030

Liver

Chronic

EA_Pp_53685a

Werner

syndromehomologue

�1� 47

0� 02130

Liver

Chronic

EA_Pp_55682a

Zgc:64119

�1� 49

0� 01440

Liver

Chronic

EA_Pp_63638a

Chem

okineligand20

�1� 50

0� 02650

Liver

Chronic

EA_Pp_61082a

26-29kD-proteinase

protein

�1� 50

0� 03060

Liver

Chronic

EA_Pp_58945a

Complexin

2�1� 51

0� 02410

Liver

Chronic

EA_Pp_55398a

RAD23homologueB

�1� 51

0� 00918

Liver

Chronic

EA_Pp_53694a

Sim

ilarto


mem

ber

12

�1� 52

0� 04620

Liver

Chronic

EA_Pp_50549a

Zgc:86583

�1� 54

0� 01540

Liver

Chronic

EA_Pp_54480a

Unknown

�1� 54

0� 04100


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Chronic

EA_Pp_57824a

Cingulin

�1� 54

0� 04740

Liver

Chronic

EA_Pp_55862a

Sim

ilarto

neuronaltransm

embraneprotein

Slitrk4

�1� 55

0� 02290

Liver

Chronic

EA_Pp_52488a

Zgc:92040

�1� 55

0� 02470

Liver

Chronic

EA_Pp_53274a

Malonyl-CoA

decarboxylase

�1� 55

0� 04770

Liver

Chronic

EA_Pp_60791a

NudEnucleardistributiongeneE

homologue1

�1� 56

0� 04580

Liver

Chronic

EA_Pp_60047a

Insulin-likegrowth

factor1breceptor

�1� 58

0� 03760

Liver

Chronic

EA_Pp_67766a

Si:ch211-152c2� 3

�1� 61

0� 00460

Liver

Chronic

EA_Pp_64327a

Zgc:91890

�1� 61

0� 02180

Liver

Chronic

EA_Pp_66730a

BRF1homologue,

subunitofRNA

polymerase

III

transcriptioninitiationfactorIIIB

�1� 61

0� 01450

Liver

Chronic

EA_Pp_55694a

Collagen,typeXVIII,alpha1

�1� 62

0� 02090

Liver

Chronic

EA_Pp_61534a

Dickkopfhomologue3

�1� 63

0� 01370

Liver

Chronic

EA_Pp_52843a

Cryptochrome2b

�1� 65

0� 01380

Liver

Chronic

EA_Pp_68737a

Zgc:92038

�1� 66

0� 03930

Liver

Chronic

EA_Pp_50235a


1homologue

�1� 66

0� 02000

Liver

Chronic

EA_Pp_69363a

Dolichyl-di-phosphooligosaccharide-protein

glycotransferase

�1� 66

0� 02790

Liver

Chronic

EA_Pp_51692a

RIK

EN

cDNA

A930038C07gene

�1� 67

0� 04500

Liver

Chronic

EA_Pp_63841a

Seizure-related6homologue-like2

�1� 67

0� 00877

Liver

Chronic

EA_Pp_63223a

Unknown

�1� 67

0� 03420

Liver

Chronic

EA_Pp_59567a

DNA

methyltransferase

3B

�1� 69

0� 02690

Liver

Chronic

EA_Pp_65534a

Amyloid

betaprecursorprotein

binding,familyB,mem

ber

2�1� 71

0� 01110

Liver

Chronic

EA_Pp_58869a

SWI–SNFrelated,matrix

associated,actin-dependent

regulatorofchromatin,subfamilyE,mem

ber

1�1� 71

0� 03890

Liver

Chronic

EA_Pp_54225a

Sim

ilarto

PGC-1-relatedco-activator

�1� 73

0� 00603

Liver

Chronic

EA_Pp_50593a

Olfactomedin

3�1� 75

0� 04350

Liver

Chronic

EA_Pp_52806a

Ephrin-B2

�1� 77

0� 03740

Liver

Chronic

EA_Pp_58881a

Phosphatidylserinesynthase

1�1� 80

0� 01070


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Chronic

EA_Pp_58604a

Caveolin3

�1� 81

0� 01430

Liver

Chronic

EA_Pp_55807a

Zgc:63736

�1� 82

0� 02890

Liver

Chronic

EA_Pp_64690a

Unknown

�1� 83

0� 04460

Liver

Chronic

EA_Pp_52975a

Sim

ilarto

DEAH

boxpolypeptide30isoform

2�1� 84

0� 01140

Liver

Chronic

EA_Pp_55736a

Vacuolarprotein

sorting52

�1� 86

0� 01240

Liver

Chronic

EA_Pp_63218a

Unknown

�1� 88

0� 03140

Liver

Chronic

EA_Pp_50485a

Zgc:77395

�1� 91

0� 02730

Liver

Chronic

EA_Pp_68019a

KIA

A0284

�1� 91

0� 02680

Liver

Chronic

EA_Pp_65187a

Sim

ilarto

chromosome13open

readingframe14

�1� 95

0� 02140

Liver

Chronic

EA_Pp_56230a

PRP19–PSO4homologue

�1� 96

0� 00920

Liver

Chronic

EA_Pp_51942a

Wntinhibitory

factor1

�1� 98

0� 04230

Liver

Chronic

EA_Pp_54333a

Zgc:91900

�2� 04

0� 01910

Liver

Chronic

EA_Pp_69419a

Sim

ilarto

phospholipase

D3

�2� 04

0� 02120

Liver

Chronic

EA_Pp_51474a

Nervegrowth

factor,betapolypeptide

�2� 05

0� 03400

Liver

Chronic

EA_Pp_54330a

Solute

carrierorganic

aniontransporter

family,mem

ber

1B3

�2� 06

0� 02640

Liver

Chronic

EA_Pp_51081a

Aquaporin3

�2� 12

0� 02440

Liver

Chronic

EA_Pp_65036a

Solute

carrierfamily1,mem

ber

4�2� 17

0� 00229

Liver

Chronic

EA_Pp_70946a

Hypotheticalprotein

LOC561486

�2� 17

0� 00454

Liver

Chronic

EA_Pp_62246a

Zgc:92652

�2� 20

0� 02040

Liver

Chronic

EA_Pp_60610a

AnkyrinrepeatandFYVE

domain-containing1

�2� 27

0� 02960

Liver

Chronic

EA_Pp_58814a

Solute

carrierfamily23,mem

ber

2�2� 30

0� 01190

Liver

Chronic

EA_Pp_58888a

Bagpipehomeoboxgene1homologue

�2� 30

0� 04580

Liver

Chronic

EA_Pp_50075a

Apoptosis-inducingfactor-likemitochondrion-associated

inducerofdeath

�2� 43

0� 00972

Liver

Chronic

EA_Pp_58775a


TPase,6

�2� 44

0� 02280

Liver

Chronic

EA_Pp_53013a

Zgc:56164

�2� 48

0� 01800

Liver

Chronic

EA_Pp_70996a

Tubulin,beta6

�2� 50

0� 00378


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Liver

Chronic

EA_Pp_57419a

Hypotheticalprotein

FLJ22349

�2� 55

0� 04350

Liver

Chronic

EA_Pp_60562a

MCM6minichromosomemaintenance

deficient6

�2� 61

0� 03860

Liver

Chronic

EA_Pp_66996a

Interferon-inducedprotein

44-like

�2� 67

0� 03290

Liver

Chronic

EA_Pp_56237a

Chaperonin

containingTCP1,subunit5

�3� 04

0� 00463

Liver

Chronic

EA_Pp_66323a

Zgc:85889

�3� 07

0� 04350

Liver

Chronic

EA_Pp_69169a

EF-handdomain-containing1

�3� 28

0� 03930

Liver

Chronic

EA_Pp_69194a

Ubiquitin-like7

�3� 78

0� 01770

Liver

Chronic

EA_Pp_65566a

Sim

ilarto

CC

chem

okine-1

�4� 55

0� 03430

Liver

Chronic

EA_Pp_60220a

MHC

Class

IUBA

gene

�7� 21

0� 04570

Gonad

Acute

EA_Pp_52403a

MHC

Class

IUFA

Gene

7� 01

0� 01840

Gonad

Acute

EA_Pp_64510a

Sim

ilarto

contactin

3precursor

5� 03

0� 01930

Gonad

Acute

EA_Pp_67099a

Myocilin

3� 63

0� 00158

Gonad

Acute

EA_Pp_55599a

Unknown

3� 49

0� 02600

Gonad

Acute

EA_Pp_68625a

Zgc:92715

3� 04

0� 02480

Gonad

Acute

EA_Pp_56080a

Transm

embraneprotein

withEGF-likeandtw

ofollistatin-likedomains2

2� 86

0� 01860

Gonad

Acute

EA_Pp_60964a

Calcium

channel,voltage-dependent,gammasubunit2

2� 81

0� 04900

Gonad

Acute

EA_Pp_53749a

Tissueinhibitorofmetalloproteinase

22� 71

0� 03140

Gonad

Acute

EA_Pp_68240a

RAB9B,mem

ber

RASoncogenefamily

2� 56

0� 02290

Gonad

Acute

EA_Pp_57148a

Sim

ilarto

cadherin

7,type2preproprotein

2� 48

0� 02970

Gonad

Acute

EA_Pp_51521a

Unknown

2� 46

0� 02430

Gonad

Acute

EA_Pp_71037a

C1qAndtumournecrosisfactor-relatedprotein

12� 46

0� 00318

Gonad

Acute

EA_Pp_51452a

XCR1protein

2� 44

0� 00678

Gonad

Acute

EA_Pp_63452a

Guaninedeaminase

2� 35

0� 04190

Gonad

Acute

EA_Pp_64712a

Solute

carrierfamily7,mem

ber

62� 27

0� 03840

Gonad

Acute

EA_Pp_62477a

Sim

ilarto

(segment2of2)Versicancore

protein

precursor

2� 25

0� 00163

Gonad

Acute

EA_Pp_52194a

Hypotheticalprotein

LOC402824

2� 14

0� 01940


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Acute

EA_Pp_60233a

Zgc:112105

2� 11

0� 01690

Gonad

Acute

EA_Pp_57723a

Hypotheticalprotein

LOC564539

2� 07

0� 03300

Gonad

Acute

EA_Pp_51228a

Adenylate

kinase

51� 99

0� 00787

Gonad

Acute

EA_Pp_53108a

WD

repeatdomain

23

1� 95

0� 00550

Gonad

Acute

EA_Pp_64820a


1� 91

0� 01260

Gonad

Acute

EA_Pp_57174a

Ets

variantgene7

1� 89

0� 02990

Gonad

Acute

EA_Pp_53874a

Sim

ilarto

GLIS

familyzincfinger

11� 84

0� 02800

Gonad

Acute

EA_Pp_70846a

Suppressorofcytokinesignalling1

1� 84

0� 02310

Gonad

Acute

EA_Pp_69724a

Periostin,osteoblast-specificfactor

1� 81

0� 02290

Gonad

Acute

EA_Pp_59608a

Hepaticleukaem

iafactor

1� 79

0� 04400

Gonad

Acute

EA_Pp_56803a

Unknown

1� 77

0� 00616

Gonad

Acute

EA_Pp_57014a

Sb:cb742

1� 75

0� 02410

Gonad

Acute

EA_Pp_52682a

Src-likeadaptor

1� 65

0� 01720

Gonad

Acute

EA_Pp_67234a

Pallidin

1� 65

0� 01130

Gonad

Acute

EA_Pp_55055a

MGC80698protein

1� 57

0� 00231

Gonad

Acute

EA_Pp_68629a

CCAAT–enhancer-bindingprotein,alpha

1� 55

0� 03440

Gonad

Acute

EA_Pp_61703a

Genemodel

1362,

1� 53

0� 02860

Gonad

Acute

EA_Pp_55635a

Uridine–cytidinekinase

1-like1

1� 45

0� 02830

Gonad

Acute

EA_Pp_65550a

Proopiomelanocortin

A1� 44

0� 04400

Gonad

Acute

EA_Pp_52989a

Celldivisioncycle-associated7

1� 38

0� 02910

Gonad

Acute

EA_Pp_57810a

Sim

ilarto

rhoguaninenucleotideexchangefactor6

1� 37

0� 00848

Gonad

Acute

EA_Pp_53977a

DEPdomain-containing6

1� 35

0� 00323

Gonad

Acute

EA_Pp_53575a

Muscle

RASoncogenehomologue

1� 31

0� 03730

Gonad

Acute

EA_Pp_65055a

V-ets

erythroblastosisvirusE26oncogenehomologue2

1� 27

0� 00504

Gonad

Acute

EA_Pp_68552a

Sim

ilarto

majorfacilitatorsuperfamilydomain-containing1

1� 24

0� 01850

Gonad

Acute

EA_Pp_50389a

Tetraspanin

41� 24

0� 00428

Gonad

Acute

EA_Pp_70675a

Interleukin

22receptor,alpha2

1� 22

0� 02840


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Acute

EA_Pp_53011a

Si:ch211-226m16� 2

1� 22

0� 03730

Gonad

Acute

EA_Pp_56568a

Zgc:92184

1� 21

0� 03940

Gonad

Acute

EA_Pp_58135a

Unknown

1� 21

0� 03360

Gonad

Acute

EA_Pp_65996a

Solute

carrierfamily39,mem

ber

41� 21

0� 02280

Gonad

Acute

EA_Pp_68894a

Coenzyme-A

synthase

1� 20

0� 01030

Gonad

Acute

EA_Pp_52004a

MyosinIX

B1� 20

0� 01510

Gonad

Acute

EA_Pp_50790a

Src

homology2domain-containingF

1� 20

0� 04900

Gonad

Acute

EA_Pp_68866a

Sim

ilarto

GTPase,IM

APfamilymem

ber

1� 19

0� 01470

Gonad

Acute

EA_Pp_57586a

Zgc:85979

1� 19

0� 03300

Gonad

Acute

EA_Pp_66539a

Hypotheticalprotein

DKFZp434G156

1� 18

0� 03360

Gonad

Acute

EA_Pp_54612a

Gelsolinlike1

1� 18

0� 01050

Gonad

Acute

EA_Pp_67376a

Chromatinaccessibilitycomplex1

1� 16

0� 04820

Gonad

Acute

EA_Pp_53858a

Sim

ilarto

serine–threonine-protein

kinase

PLK2

1� 16

0� 04270

Gonad

Acute

EA_Pp_69330a

Interferonregulatory

factor7

1� 16

0� 03750

Gonad

Acute

EA_Pp_56237a

Chaperonin

containingTCP1,subunit5

1� 16

0� 01300

Gonad

Acute

EA_Pp_63802a

Sim

ilarto

retinoic

acidinducible

protein

31� 13

0� 00712

Gonad

Acute

EA_Pp_58414a

Procollagen,typeXXVII,alpha1

1� 13

0� 03630

Gonad

Acute

EA_Pp_53694a

Sim

ilarto


mem

ber

12

1� 11

0� 02940

Gonad

Acute

EA_Pp_55712a

Unknown

1� 09

0� 01790

Gonad

Acute

EA_Pp_52065a

Sim

ilarto

carcinoem

bryonic

antigen-relatedcell

adhesionmolecule

1� 09

0� 04950

Gonad

Acute

EA_Pp_60784a

Zgc:85888

1� 09

0� 01320

Gonad

Acute

EA_Pp_63944a

Unknown

1� 07

0� 02560

Gonad

Acute

EA_Pp_55270a

E74-likefactor4

1� 07

0� 04660

Gonad

Acute

EA_Pp_69575a

ForkheadboxL2

1� 07

0� 04570

Gonad

Acute

EA_Pp_52448a

Unknown

1� 06

0� 04490


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Acute

EA_Pp_67128a

Zincfinger

protein

297B

1� 05

0� 02200

Gonad

Acute

EA_Pp_50528a

H1histonefamily,mem

ber

X1� 04

0� 01260

Gonad

Acute

EA_Pp_61440a

Zgc:77059

1� 03

0� 00457

Gonad

Acute

EA_Pp_71148a

Jumonjidomain-containing3

1� 02

0� 03850

Gonad

Acute

EA_Pp_54883a

RAB27A,mem

ber

RASoncogenefamily

1� 02

0� 04940

Gonad

Acute

EA_Pp_60764a

Glycoprotein

21� 02

0� 01300

Gonad

Acute

EA_Pp_63176a

Breast

carcinomaamplified

sequence

2�1� 01

0� 03860

Gonad

Acute

EA_Pp_59755a

Zgc:101737

�1� 01

0� 00294

Gonad

Acute

EA_Pp_58589a

Ets

variantfene4

�1� 01

0� 00797

Gonad

Acute

EA_Pp_52815a

Hypotheticalprotein

LOC569123

�1� 01

0� 01430

Gonad

Acute

EA_Pp_55098a

Glutamine-rich

1�1� 01

0� 00142

Gonad

Acute

EA_Pp_69634a

Septin2

�1� 01

0� 01030

Gonad

Acute

EA_Pp_51164a

Hypotheticalprotein

MGC83548

�1� 01

0� 03530

Gonad

Acute

EA_Pp_63277a

Nipped-B

homologue

�1� 01

0� 02170

Gonad

Acute

EA_Pp_62697a

Zgc:92585

�1� 01

0� 03390

Gonad

Acute

EA_Pp_57754a

SMC1structuralmaintenance

ofchromosomes

1-like1

�1� 01

0� 03700

Gonad

Acute

EA_Pp_56827a

RIK

EN

cDNA

2310003C23gene

�1� 02

0� 01010

Gonad

Acute

EA_Pp_55215a

Origin

recognitioncomplex,subunit3-like

�1� 02

0� 02120

Gonad

Acute

EA_Pp_68290a

Calcium-sensingreceptor

�1� 02

0� 03680

Gonad

Acute

EA_Pp_51902a

Ornithineaminotransferase

�1� 02

0� 04470

Gonad

Acute

EA_Pp_58287a

Hypotheticalprotein

LOC555871

�1� 03

0� 02510

Gonad

Acute

EA_Pp_64892a

Zgc:100787

�1� 03

0� 03560

Gonad

Acute

EA_Pp_50643a

Down-regulatoroftranscription1,TBP-binding

�1� 03

0� 00328

Gonad

Acute

EA_Pp_56912a

Neuraladhesionmolecule

L1� 2

�1� 04

0� 02670

Gonad

Acute

EA_Pp_67114a

Unknown

�1� 05

0� 03790

Gonad

Acute

EA_Pp_63083a

Zgc:101661

�1� 05

0� 04910

Gonad

Acute

EA_Pp_71177a

G-protein-coupledreceptor175

�1� 05

0� 02700


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Acute

EA_Pp_64860a

Genemodel

1564,

�1� 06

0� 03560

Gonad

Acute

EA_Pp_60302a

Zincfinger

protein

133

�1� 06

0� 03020

Gonad

Acute

EA_Pp_58422a

Unknown

�1� 07

0� 01290

Gonad

Acute

EA_Pp_51778a

Sim

ilarto

ETAA16protein

�1� 07

0� 02900

Gonad

Acute

EA_Pp_53170a

Sim

ilarto

PiggyBactransposable

elem

entderived

5�1� 08

0� 00935

Gonad

Acute

EA_Pp_68853a

Sestrin

2�1� 09

0� 03260

Gonad

Acute

EA_Pp_59854a

Sim

ilarto

myomegalin

�1� 09

0� 04640

Gonad

Acute

EA_Pp_55906a

Zgc:55549

�1� 09

0� 04920

Gonad

Acute

EA_Pp_58120a

Tumoursuppressorcandidate

3�1� 09

0� 00397

Gonad

Acute

EA_Pp_53894a

Unknown

�1� 09

0� 01200

Gonad

Acute

EA_Pp_71172a

Sim

ilarto

mitogen-activatedprotein

kinase

kinase

kinase

5�1� 10

0� 00492

Gonad

Acute

EA_Pp_55927a

Acetyl-CoA

acetyltransferase

2�1� 10

0� 02910

Gonad

Acute

EA_Pp_68683a

Phenylalanine-tR

NA

synthetase-like,

betasubunit

�1� 10

0� 02970

Gonad

Acute

EA_Pp_62924a

Fuse-bindingprotein-interactingrepressor

�1� 10

0� 02640

Gonad

Acute

EA_Pp_57451a

5-m

ethyltetrahydrofolate-homocysteinemethyltransferase

�1� 10

0� 03050

Gonad

Acute

EA_Pp_64871a

Solute

carrierfamily2,mem

ber

9�1� 11

0� 01790

Gonad

Acute

EA_Pp_60965a

Unknown

�1� 11

0� 02680

Gonad

Acute

EA_Pp_59383a

KIA

A0841

�1� 12

0� 02400

Gonad

Acute

EA_Pp_62208a

Hypotheticalprotein

FLJ20641

�1� 12

0� 03250

Gonad

Acute

EA_Pp_67029a

Ewingsarcomabreakpointregion1

�1� 12

0� 00320

Gonad

Acute

EA_Pp_57086a

Hypotheticalprotein

LOC402865

�1� 13

0� 01220

Gonad

Acute

EA_Pp_55998a

Sim

ilarto

meningiomaexpressed

antigen

5�1� 13

0� 03640

Gonad

Acute

EA_Pp_66130a

Cystathioninebeta-synthase

�1� 15

0� 01200

Gonad

Acute

EA_Pp_58495a

Buddinguninhibited

bybenzimidazoles3homologue

�1� 15

0� 01290

Gonad

Acute

EA_Pp_62239a

Tubulin,gammacomplexassociatedprotein

2�1� 15

0� 01420

Gonad

Acute

EA_Pp_67397a

Polymerase

IIpolypeptideH

�1� 15

0� 02670

Gonad

Acute

EA_Pp_51854a

DNA

segment,Chr15,ERATO

Doi785,expressed

�1� 16

0� 02760


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Acute

EA_Pp_58077a

RIK

EN

cDNA

1600015H20gene

�1� 16

0� 04470

Gonad

Acute

EA_Pp_55028a

Im:7145273

�1� 16

0� 00578

Gonad

Acute

EA_Pp_65383a


14

�1� 16

0� 01880

Gonad

Acute

EA_Pp_67077a

LipomaHMGIC

fusionpartner

�1� 17

0� 02480

Gonad

Acute

EA_Pp_53072a

Kinetochore-associated1

�1� 18

0� 03120

Gonad

Acute

EA_Pp_52970a

Enhancerofzestehomologue2

�1� 19

0� 01670

Gonad

Acute

EA_Pp_59164a

Unknown

�1� 19

0� 02350

Gonad

Acute

EA_Pp_68807a

Collagen,typeI,alpha2

�1� 19

0� 03540

Gonad

Acute

EA_Pp_61468a

Squamouscellcarcinomaantigen

recognised

byT

cells

�1� 19

0� 01830

Gonad

Acute

EA_Pp_57186a

Glutamate

oxaloacetate

transaminase

1,soluble

�1� 19

0� 02150

Gonad

Acute

EA_Pp_58911a

6-phosphofructo-2-kinase–fructose-2,6-biphosphatase

1�1� 19

0� 00785

Gonad

Acute

EA_Pp_55124a

Sim

ilarto

stem

cellgrowth

factorprecursor

�1� 19

0� 03530

Gonad

Acute

EA_Pp_50623a

Collagen

typeXVIII,alpha1

�1� 19

0� 03870

Gonad

Acute

EA_Pp_71185a

Hypotheticalprotein

LOC562594

�1� 20

0� 02580

Gonad

Acute

EA_Pp_58789a

Fanconianaem

ia,complementationgroupD2

�1� 20

0� 03960

Gonad

Acute

EA_Pp_51065a

Unknown

�1� 21

0� 00685

Gonad

Acute

EA_Pp_64126a

Hypotheticalprotein

LOC443642

�1� 22

0� 02520

Gonad

Acute

EA_Pp_65361a

Zgc:92869

�1� 22

0� 03020

Gonad

Acute

EA_Pp_55557a

RAD51homologue

�1� 22

0� 02940

Gonad

Acute

EA_Pp_55262a

Polymerase

IIpolypeptideJ,

13� 3

kDa

�1� 23

0� 02370

Gonad

Acute

EA_Pp_70769a

Sim

ilarto

nucleoprotein

TPR

�1� 25

0� 00561

Gonad

Acute

EA_Pp_57894a

Wu:fi37d07

�1� 25

0� 01910

Gonad

Acute

EA_Pp_56221a

DNA

segment,Chr2,ERATO

Doi435,expressed

�1� 26

0� 01980

Gonad

Acute

EA_Pp_65508a

Zgc:101819

�1� 26

0� 02550

Gonad

Acute

EA_Pp_52574a

LSM5homologue,

U6sm

allnuclearRNA

associated

�1� 27

0� 03750

Gonad

Acute

EA_Pp_58674a

Zgc:85946

�1� 27

0� 02230

Gonad

Acute

EA_Pp_54753a

Guaninenucleotide-bindingprotein,betapolypeptide2-like1

�1� 30

0� 03440


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Acute

EA_Pp_64150a

Cyclin

G2

�1� 30

0� 03140

Gonad

Acute

EA_Pp_69115a

CCR4-N

OTtranscriptioncomplex,subunit6

�1� 31

0� 01600

Gonad

Acute

EA_Pp_61434a

Zgc:55316

�1� 31

0� 02430

Gonad

Acute

EA_Pp_50801a


delta

isomerase

1�1� 33

0� 03550

Gonad

Acute

EA_Pp_61523a

Leucine-rich

repeat-containing40

�1� 34

0� 00415

Gonad

Acute

EA_Pp_59665a


�1� 34

0� 00638

Gonad

Acute

EA_Pp_70946a

Hypotheticalprotein

LOC561486

�1� 34

0� 04000

Gonad

Acute

EA_Pp_56911a

Tyrosyl-tR

NA

synthetase

�1� 35

0� 04120

Gonad

Acute

EA_Pp_51986a

WD

repeatdomain

12

�1� 35

0� 01010

Gonad

Acute

EA_Pp_64707a

RIK

EN

cDNA

1190005F20gene

�1� 37

0� 03080

Gonad

Acute

EA_Pp_51546a


kinase

13

�1� 37

0� 03920

Gonad

Acute

EA_Pp_63165a

Tubulin,alpha,ubiquitous

�1� 37

0� 02610

Gonad

Acute

EA_Pp_60213a

Unknown

�1� 39

0� 01390

Gonad

Acute

EA_Pp_60106a

Tetratricopeptiderepeatdomain

3�1� 40

0� 04130

Gonad

Acute

EA_Pp_54809a

TRAF-interactingprotein

�1� 42

0� 00513

Gonad

Acute

EA_Pp_68359a


�1� 42

0� 01750

Gonad

Acute

EA_Pp_60129a

Monooxygenase,DBH-like1

�1� 42

0� 00874

Gonad

Acute

EA_Pp_60101a

Sim

ilarto

KIA

A1276protein

�1� 43

0� 01810

Gonad

Acute

EA_Pp_54201a

Histone3,H2ba

�1� 44

0� 00669

Gonad

Acute

EA_Pp_63208a

Flotillin

1b

�1� 45

0� 03290

Gonad

Acute

EA_Pp_50066a

XIA

P-associatedfactor1

�1� 46

0� 04440

Gonad

Acute

EA_Pp_62783a

SUMO-1-activatingenzymesubunit2

�1� 48

0� 03920

Gonad

Acute

EA_Pp_70184a

Zgc:65956

�1� 49

0� 04770

Gonad

Acute

EA_Pp_64327a

Si:ch211-152c2� 3

�1� 51

0� 00477

Gonad

Acute

EA_Pp_70182a

Snf2-relatedCBPactivatorprotein

�1� 52

0� 00419

Gonad

Acute

EA_Pp_58573a

Unknown

�1� 54

0� 00875

Gonad

Acute

EA_Pp_58910a

Sim

ilarto

UPF0143protein

C14orf1

�1� 54

0� 02990


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Acute

EA_Pp_62663a

Hypotheticalprotein

MGC83251

�1� 55

0� 00646

Gonad

Acute

EA_Pp_57567a

Nucleoporin50

�1� 57

0� 01330

Gonad

Acute

EA_Pp_55307a

Zgc:56065

�1� 62

0� 04670

Gonad

Acute

EA_Pp_52309a

Zgc:63647

�1� 64

0� 04720

Gonad

Acute

EA_Pp_53557a

Translocatedpromoterregion

�1� 66

0� 02530

Gonad

Acute

EA_Pp_53929a

Phosphorylase,glycogen;muscle

�1� 68

0� 02230

Gonad

Acute

EA_Pp_51174a

Zgc:100947

�1� 69

0� 00701

Gonad

Acute

EA_Pp_64154a

Chromosome18open

readingframe54

�1� 72

0� 00553

Gonad

Acute

EA_Pp_69226a

CDC37celldivisioncycle37homologue

�1� 74

0� 00341

Gonad

Acute

EA_Pp_69396a

Leucine-rich

repeats

anddeath

domain

containing

�1� 77

0� 01440

Gonad

Acute

EA_Pp_65758a

ENSANGP00000021368

�1� 82

0� 04590

Gonad

Acute

EA_Pp_54008a

Zgc:55876

�1� 83

0� 02050

Gonad

Acute

EA_Pp_50460a

Hypotheticalprotein

LOC555377

�1� 86

0� 02160

Gonad

Acute

EA_Pp_65288a

Splicingfactor,arginine–serine-rich

7� 35kDa

�1� 91

0� 01380

Gonad

Acute

EA_Pp_68294a

CoagulationfactorV

�1� 93

0� 01420

Gonad

Acute

EA_Pp_66133a

Leucocyte

receptorcluster

mem

ber

4�2� 01

0� 03830

Gonad

Acute

EA_Pp_51012a

Unknown

�2� 02

0� 02110

Gonad

Acute

EA_Pp_67859a

Unknown

�2� 03

0� 00578

Gonad

Acute

EA_Pp_65462a

Cartilageinterm

ediate

layer

protein,nucleotide

pyrophosphohydrolase

�2� 06

0� 04370

Gonad

Acute

EA_Pp_59188a

Sim

ilarto

neuromedin

Bprecursor–rat

�2� 08

0� 01380

Gonad

Acute

EA_Pp_65899a

Adiponectin,C1Q

andcollagen

domain

containing

�2� 16

0� 00061

Gonad

Acute

EA_Pp_59573a

CCR4,carboncatabolite

repression4-like

�2� 16

0� 01360

Gonad

Acute

EA_Pp_69182a

Sim

ilarto

LOC496079protein

�2� 20

0� 00984

Gonad

Acute

EA_Pp_57046a

Sim

ilarto

embigin

homologue

�2� 25

0� 02390

Gonad

Acute

EA_Pp_56200a

Neurobeachin

�2� 34

0� 01290

Gonad

Acute

EA_Pp_52836a

Ectonucleosidetriphosphate

diphosphohydrolase

2�2� 53

0� 00231


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Acute

EA_Pp_51946a

Potassium

channel,subfamilyK,mem

ber

9�2� 54

0� 01480

Gonad

Acute

EA_Pp_58630a

Zgc:110216

�2� 72

0� 01500

Gonad

Acute

EA_Pp_69650a

SRY-box30

�2� 86

0� 04530

Gonad

Acute

EA_Pp_69200a

Steroidogenic

acute

regulatory

protein

�3� 06

0� 02980

Gonad

Acute

EA_Pp_61640a

Aquaporin8

�3� 12

0� 00365

Gonad

Acute

EA_Pp_55159a

Calcium–calm

odulin-dependentprotein

kinase

ID�3� 40

0� 01410

Gonad

Acute

EA_Pp_67799a


U-like1

�4� 71

0� 02410

Gonad

Acute

EA_Pp_59995a

Unknown

�5� 00

0� 00046

Gonad

Acute

EA_Pp_60220a

MHC

class

IUBA

gene

�9� 64

0� 00056

Gonad

Chronic

EA_Pp_60138a

Haem

oglobin

alphaem

bryonic-1

2� 71

0� 00984

Gonad

Chronic

EA_Pp_67445a


2� 66

0� 03020

Gonad

Chronic

EA_Pp_69275a

Zgc:92880

2� 42

0� 01090

Gonad

Chronic

EA_Pp_51389a


2� 31

0� 01450

Gonad

Chronic

EA_Pp_54242a

Diacylglycerolkinase,delta

130kDa

2� 11

0� 01870

Gonad

Chronic

EA_Pp_53837a

Slingshothomologue1

1� 76

0� 04110

Gonad

Chronic

EA_Pp_53793a

Zgc:85969

1� 60

0� 04680

Gonad

Chronic

EA_Pp_55632a

Solute

carrierfamily31,mem

ber

21� 52

0� 03070

Gonad

Chronic

EA_Pp_53291a

Chloridechannel

CLIC

-like1

1� 48

0� 04590

Gonad

Chronic

EA_Pp_61828a

Kinesin

21� 48

0� 00395

Gonad

Chronic

EA_Pp_69293a

FK506-bindingprotein

51� 44

0� 00228

Gonad

Chronic

EA_Pp_56320a


1� 39

0� 04030

Gonad

Chronic

EA_Pp_53875a

CAMP-regulatedphosphoprotein

19

1� 36

0� 00090

Gonad

Chronic

EA_Pp_54250a

Anti-dorsalizingmorphogenic

protein

1� 35

0� 04500

Gonad

Chronic

EA_Pp_59431a


1� 30

0� 02400

Gonad

Chronic

EA_Pp_52426a

FK506-bindingprotein

51� 28

0� 04550

Gonad

Chronic

EA_Pp_53807a

Tryptophan-richbasicprotein

1� 28

0� 01550

Gonad

Chronic

EA_Pp_61645a

Arylhydrocarbonreceptor1b

1� 14

0� 04440


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Chronic

EA_Pp_68038a

Si:rp71-1f1� 3

1� 11

0� 02100

Gonad

Chronic

EA_Pp_66875a

Activin

receptorIIb

1� 10

0� 03300

Gonad

Chronic

EA_Pp_52121a

Latexin

1� 09

0� 03720

Gonad

Chronic

EA_Pp_62179a

Opsin1,short-w

avesensitive2

1� 08

0� 04300

Gonad

Chronic

EA_Pp_56079a

Sim

ilarto

hypotheticaltestisprotein

from

macaque

1� 08

0� 02120

Gonad

Chronic

EA_Pp_50541a

Unknown

1� 06

0� 03010

Gonad

Chronic

EA_Pp_54049a

Sim

ilarto

typeII

phosphatidylinositolphosphatekinase-alpha

1� 05

0� 02940

Gonad

Chronic

EA_Pp_61777a

Unknown

1� 03

0� 01310

Gonad

Chronic

EA_Pp_68611a

Unknown

1� 02

0� 03910

Gonad

Chronic

EA_Pp_61521a

XKellbloodgroupprecursor-relatedfamilymem

ber

6homologue

�1� 00

0� 04490

Gonad

Chronic

EA_Pp_69850a

Zgc:77732

�1� 00

0� 00253

Gonad

Chronic

EA_Pp_53518a

Sim

ilarto

MGC81609protein

�1� 00

0� 02050

Gonad

Chronic

EA_Pp_52054a

Unknown

�1� 00

0� 02950

Gonad

Chronic

EA_Pp_58978a

Tetraspanin

5�1� 00

0� 03130

Gonad

Chronic

EA_Pp_51190a

RIK

EN

cDNA

6332401O19gene

�1� 01

0� 00860

Gonad

Chronic

EA_Pp_57083a

One-cutdomain,familymem

ber

1�1� 01

0� 01050

Gonad

Chronic

EA_Pp_55507a

Properdin

Pfactor,complement

�1� 01

0� 02640

Gonad

Chronic

EA_Pp_53965a

Unknown

�1� 02

0� 03290

Gonad

Chronic

EA_Pp_57858a

Unknown

�1� 03

0� 03790

Gonad

Chronic

EA_Pp_67214a

Sim

ilartoB-celllymphoma3-encoded

protein

�1� 03

0� 04960

Gonad

Chronic

EA_Pp_52573a

TAK1-bindingprotein

1�1� 04

0� 01890

Gonad

Chronic

EA_Pp_62117a

SRY-boxcontaininggene10

�1� 04

0� 03560

Gonad

Chronic

EA_Pp_51089a

Transcriptionfactor4

�1� 04

0� 00812

Gonad

Chronic

EA_Pp_56122a

Unknown

�1� 04

0� 02270

Gonad

Chronic

EA_Pp_62316a

LIM

domain-binding2

�1� 05

0� 03450

Gonad

Chronic

EA_Pp_53055a

Unknown

�1� 06

0� 03100


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Chronic

EA_Pp_50302a

Unknown

�1� 06

0� 03700

Gonad

Chronic

EA_Pp_51419a

Sim

ilarto

hypotheticalgenesupported

byBC039313

�1� 09

0� 04410

Gonad

Chronic

EA_Pp_63086a

Acetyl-coenzyme-A

carboxylase

beta

�1� 10

0� 01150

Gonad

Chronic

EA_Pp_66562a

Proline,

glutamic

acidandleucine-rich

protein

1�1� 10

0� 03250

Gonad

Chronic

EA_Pp_65931a

Sim

ilarto

elongationfactor1-delta

�1� 10

0� 02560

Gonad

Chronic

EA_Pp_56333a

Epidermalgrowth

factorreceptor

�1� 11

0� 00551

Gonad

Chronic

EA_Pp_63897a

Chromosome11open

readingframe9

�1� 11

0� 03130

Gonad

Chronic

EA_Pp_70706a

Neurogenic

differentiation1

�1� 12

0� 02260

Gonad

Chronic

EA_Pp_58294a

Ornithinetranscarbamylase

�1� 12

0� 03860

Gonad

Chronic

EA_Pp_59819a

Unknown

�1� 13

0� 04140

Gonad

Chronic

EA_Pp_60930a

Nasalem

bryonic

LHRH

factor

�1� 13

0� 04430

Gonad

Chronic

EA_Pp_54679a

LRP16protein

�1� 14

0� 00276

Gonad

Chronic

EA_Pp_60077a

Sim

ilarto

predictedCDS,Zn-finger,CCHC

typeandRNA-

directedDNA

polymerase

andintegrase,catalyticdomain-

containingprotein

familymem

ber

�1� 14

0� 03750

Gonad

Chronic

EA_Pp_53307a

Sim

ilarto

discs

largehomologue7

�1� 15

0� 02920

Gonad

Chronic

EA_Pp_55276a

Sim

ilarto

calcium-independentalpha-latrotoxin

receptor

homologue3

�1� 16

0� 02310

Gonad

Chronic

EA_Pp_61350a

Unknown

�1� 16

0� 03090

Gonad

Chronic

EA_Pp_62214a

Unknown

�1� 16

0� 01570

Gonad

Chronic

EA_Pp_53960a

Zgc:64076

�1� 17

0� 01080

Gonad

Chronic

EA_Pp_66413a

Sim

ilarto

connectorenhancerofKSR2A

�1� 18

0� 02170

Gonad

Chronic

EA_Pp_54817a

Unknown

�1� 19

0� 00389

Gonad

Chronic

EA_Pp_63168a

Unknown

�1� 21

0� 01950

Gonad

Chronic

EA_Pp_57984a

cDNA

sequence

BC060631

�1� 23

0� 01680

Gonad

Chronic

EA_Pp_62330a

Cysteinylleukotrienereceptor2

�1� 23

0� 01100

Gonad

Chronic

EA_Pp_54978a

Complexin

4�1� 24

0� 01520


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Chronic

EA_Pp_58380a

Macrophagereceptorwithcollagenousstructure

�1� 25

0� 04930

Gonad

Chronic

EA_Pp_52409a

Sim

ilarto

RIK

EN

cDNA

8430427H17gene

�1� 26

0� 02090

Gonad

Chronic

EA_Pp_57136a

Sim

ilarto

CXC

chem

okine

�1� 26

0� 02820

Gonad

Chronic

EA_Pp_61715a

Vesicle-associatedmem

braneprotein

1�1� 28

0� 04040

Gonad

Chronic

EA_Pp_70703a

HomeoboxD3

�1� 29

0� 04560

Gonad

Chronic

EA_Pp_56032a

Mem

braneprotein,palm

itoylated2

�1� 29

0� 03920

Gonad

Chronic

EA_Pp_54767a

Unknown

�1� 30

0� 00552

Gonad

Chronic

EA_Pp_54067a

Sim

ilarto

Fas-activatedserine–threoninekinase

�1� 31

0� 01280

Gonad

Chronic

EA_Pp_70488a

Bystin-like

�1� 31

0� 01660

Gonad

Chronic

EA_Pp_70355a

G-Protein-coupledreceptor35

�1� 33

0� 04260

Gonad

Chronic

EA_Pp_68906a

Unknown

�1� 34

0� 03720

Gonad

Chronic

EA_Pp_60766a

LOC468601

�1� 35

0� 00308

Gonad

Chronic

EA_Pp_55288a

Guanylylcyclase

3�1� 35

0� 03320

Gonad

Chronic

EA_Pp_68392a

Nervegrowth

factorreceptor

�1� 35

0� 03330

Gonad

Chronic

EA_Pp_68445a

Sim

ilarto

LOC496297protein

�1� 37

0� 00511

Gonad

Chronic

EA_Pp_64016a

Tweety

homologue3

�1� 37

0� 01190

Gonad

Chronic

EA_Pp_59779a

KIA

A1466gene

�1� 38

0� 00900

Gonad

Chronic

EA_Pp_67592a

Unknown

�1� 38

0� 02710

Gonad

Chronic

EA_Pp_51793a

Sim

ilarto

jumpingtranslocationbreakpoint

�1� 39

0� 01270

Gonad

Chronic

EA_Pp_70921a

Sloan-K

etteringviraloncogenehomologue

�1� 40

0� 00689

Gonad

Chronic

EA_Pp_57046a

Sim

ilarto

embigin

homologue

�1� 40

0� 02800

Gonad

Chronic

EA_Pp_63635a

Nanoshomologue1

�1� 41

0� 04100

Gonad

Chronic

EA_Pp_60742a

Zincfinger

protein

286

�1� 42

0� 01560

Gonad

Chronic

EA_Pp_52270a

Cytochrome

coxidase

subunitIII

�1� 43

0� 01050

Gonad

Chronic

EA_Pp_68682a

Zincfinger,MYM-type1

�1� 43

0� 00991

Gonad

Chronic

EA_Pp_54350a

ADP-ribosylationfactor-like6-interactingprotein

2�1� 43

0� 01310

Gonad

Chronic

EA_Pp_53034a

Sim

ilarto

protocadherin

1gammaA

2�1� 45

0� 01090


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Chronic

EA_Pp_59749a

Unknown

�1� 45

0� 02350

Gonad

Chronic

EA_Pp_55605a

Scavenger

receptorclass

B,mem

ber

1�1� 46

0� 02680

Gonad

Chronic

EA_Pp_71038a

Sim

ilarto

KIA

A1883protein

�1� 49

0� 02580

Gonad

Chronic

EA_Pp_62470a

Sim

ilarto

epidermallangerhanscellprotein

LCP1

�1� 49

0� 04030

Gonad

Chronic

EA_Pp_55387a

Paternallyexpressed

10

�1� 51

0� 00880

Gonad

Chronic

EA_Pp_64910a

Chromosome1open

readingframe70

�1� 51

0� 00470

Gonad

Chronic

EA_Pp_67013a

Unknown

�1� 52

0� 00160

Gonad

Chronic

EA_Pp_59744a

TLC

domain-containing1

�1� 52

0� 01920

Gonad

Chronic

EA_Pp_57879a

Sim

ilarto

leucine-rich

repeattransm

embranerrotein

FLRT2

precursor

�1� 53

0� 04420

Gonad

Chronic

EA_Pp_63420a

Unknown

�1� 53

0� 01790

Gonad

Chronic

EA_Pp_58820a

Unknown

�1� 53

0� 02550

Gonad

Chronic

EA_Pp_67525a

Unknown

�1� 56

0� 03050

Gonad

Chronic

EA_Pp_53257a

Unknown

�1� 57

0� 01060

Gonad

Chronic

EA_Pp_58195a

Sim

ilarto

nucleartranscriptionfactor,X-box-binding

1isoform

1�1� 58

0� 00035

Gonad

Chronic

EA_Pp_66323a

Zgc:85889

�1� 59

0� 03610

Gonad

Chronic

EA_Pp_66434a

Unknown

�1� 60

0� 03770

Gonad

Chronic

EA_Pp_58320a

Unknown

�1� 61

0� 00859

Gonad

Chronic

EA_Pp_71125a

Unknown

�1� 64

0� 01230

Gonad

Chronic

EA_Pp_52583a

Zgc:123297

�1� 66

0� 02900

Gonad

Chronic

EA_Pp_61266a

Hypotheticalprotein

�1� 67

0� 00317

Gonad

Chronic

EA_Pp_64966a

Unknown

�1� 67

0� 01550

Gonad

Chronic

EA_Pp_65520a

Sim

ilarto

oxysterol-bindingprotein-like1A

osoform

B�1� 67

0� 03430

Gonad

Chronic

EA_Pp_66936a

Glycogen

synthase

1�1� 69

0� 02800

Gonad

Chronic

EA_Pp_56381a

Tryptase

gamma1

�1� 72

0� 00745

Gonad

Chronic

EA_Pp_55862a

Zgc:92040

�1� 74

0� 00710


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Chronic

EA_Pp_63900a

Unknown

�1� 75

0� 01590

Gonad

Chronic

EA_Pp_54796a

GTPase-activatingRap/R

anGAPdomain-like4

�1� 78

0� 03310

Gonad

Chronic

EA_Pp_58205a

Zgc:110231

�1� 78

0� 04020

Gonad

Chronic

EA_Pp_57522a

Zgc:63566

�1� 79

0� 00539

Gonad

Chronic

EA_Pp_54841a

P21(C

DKN1A)-activatedkinase

4�1� 79

0� 02690

Gonad

Chronic

EA_Pp_68031a

Ventralanteriorhomeobox1

�1� 80

0� 00827

Gonad

Chronic

EA_Pp_61721a

Unknown

�1� 81

0� 00547

Gonad

Chronic

EA_Pp_56583a

Dynactin

4�1� 82

0� 00496

Gonad

Chronic

EA_Pp_65988a

Chromosome17open

readingframe44

�1� 83

0� 04870

Gonad

Chronic

EA_Pp_53306a

Cholinergic

receptor,nicotinic,betapolypeptide2

�1� 83

0� 00147

Gonad

Chronic

EA_Pp_66135a

Unknown

�1� 84

0� 03050

Gonad

Chronic

EA_Pp_67049a

Unknown

�1� 84

0� 04950

Gonad

Chronic

EA_Pp_54697a

Unknown

�1� 86

0� 03000

Gonad

Chronic

EA_Pp_67738a

RIK

EN

cDNA

2410066E13gene

�1� 87

0� 02820

Gonad

Chronic

EA_Pp_62641a

RhoGTPase-activatingprotein

1�1� 92

0� 02300

Gonad

Chronic

EA_Pp_63732a

Connectorenhancerofkinase

suppressorofRas1

�1� 94

0� 00132

Gonad

Chronic

EA_Pp_65880a

Sim

ilarto

CG1500-PA

�1� 95

0� 03110

Gonad

Chronic

EA_Pp_58775a


TPase,6

�1� 99

0� 02770

Gonad

Chronic

EA_Pp_61742a

Unknown

�2� 00

0� 00079

Gonad

Chronic

EA_Pp_57996a

Unknown

�2� 03

0� 02970

Gonad

Chronic

EA_Pp_51160a

Neuroligin

1�2� 06

0� 00388

Gonad

Chronic

EA_Pp_51077a

RIK

EN

cDNA

2310067E08gene

�2� 07

0� 04650

Gonad

Chronic

EA_Pp_69895a

Sim

ilarto

stonustoxin

betasubunit

�2� 13

0� 03000

Gonad

Chronic

EA_Pp_57101a

Gamma-aminobutyricacidreceptor,subunitdelta

�2� 15

0� 01990

Gonad

Chronic

EA_Pp_66695a

Protease

26Ssubunit,ATPase

1�2� 31

0� 02780

Gonad

Chronic

EA_Pp_57419a

Hypotheticalprotein

FLJ22349

�2� 32

0� 01190

Gonad

Chronic

EA_Pp_62849a

Sim

ilarto

CG8779-PA

�2� 44

0� 00217


# 2008 The Authors


APPENDIX

I.Continued

Tissue

Exposure

ProbeID

Genetitle

Logtw

o-fold

change

P-value

Gonad

Chronic

EA_Pp_56231a

Unknown

�2� 55

0� 03530

Gonad

Chronic

EA_Pp_62662a

Sim

ilarto

mucin5

�2� 71

0� 03950

Gonad

Chronic

EA_Pp_55621a

Unknown

�2� 73

0� 03340

Gonad

Chronic

EA_Pp_57869a

Unknown

�2� 89

0� 00653

Gonad

Chronic

EA_Pp_68609a

TranscriptionfactorAP-2

alpha

�2� 90

0� 04330

Gonad

Chronic

EA_Pp_53536a

Sim

ilarto

zonadhesin

�2� 98

0� 00217

Gonad

Chronic

EA_Pp_65566a

Sim

ilarto

CC

chem

okine-1

�3� 13

0� 03330

Gonad

Chronic

EA_Pp_62251a

Superoxidedismutase

3,extracellular

�3� 37

0� 01620

MHC,majorhistocompatibilitycomplex.


# 2008 The Authors


APPENDIX

II.Significantly*overrepresentedgeneontology(G

O)categories

amonggenes

withaltered

expressionin

response

tomethylm

er-

cury

exposure

GO

term

GO

definition

Number

altered†

Per

cent

altered

Number

unaltered

Per

cent

unaltered

P-value

Liver,acute

exposure

GO:0006457

Protein

folding

21

3� 23

135

0� 93

0� 000003

GO:0007076

Mitoticchromosomecondensation

30� 46

00� 00

0� 000078

GO:0007046

Ribosomebiogenesis

60� 92

16

0� 11

0� 000247

GO:0015031

Protein

transport

21

3� 23

210

1� 44

0� 001380

GO:0051084

Post-translationalprotein

folding

20� 31

00� 00

0� 001824

GO:0006633

Fattyacidbiosynthesis

40� 62

12

0� 08

0� 003990

GO:0008033

tRNA

processing

50� 77

21

0� 14

0� 004377

GO:0006605

Protein

targeting

81� 23

54

0� 37

0� 004703

GO:0000045

Autophagic

vacuole

form

ation

20� 31

10� 01

0� 005317

GO:0019884

Antigen

presentation,exogenousantigen

20� 31

10� 01

0� 005317

GO:0009058

Biosynthesis

71� 08

48

0� 33

0� 008618

GO:0006911

Phagocytosis,engulfment

20� 31

20� 01

0� 010334

GO:0045045

Secretory

pathway

30� 46

90� 06

0� 012807

GO:0008152

Metabolism

23

3� 54

300

2� 06

0� 016953

GO:0000059

Protein

import

into

nucleus,docking

30� 46

11

0� 08

0� 019887

GO:0007498

Mesoderm

development

30� 46

12

0� 08

0� 024084

GO:0009165

Nucleotidebiosynthesis

20� 31

50� 03

0� 033204

GO:0006888

ER

toGolgitransport

50� 77

39

0� 27

0� 038633

GO:0006364

rRNA

processing

40� 62

27

0� 19

0� 041688

GO:0006754

ATPbiosynthesis

20� 31

60� 04

0� 043037

GO:0042254

Ribosomebiogenesisandassem

bly

20� 31

60� 04

0� 043037

GO:0006486

Protein

aminoacidglycosylation

40� 62

28

0� 19

0� 046093

Liver,chronic

exposure

GO:0006605

Protein

targeting

62� 25

56

0� 37

0� 000747

GO:0006917

Inductionofapoptosis

41� 5

32

0� 21

0� 003519


# 2008 The Authors


APPENDIX

II.Continued

GO

term

GO

definition

Number

altered†

Per

cent

altered

Number

unaltered

Per

cent

unaltered

P-value

GO:0006887

Exocytosis

31� 12

17

0� 11

0� 004891

GO:0016485

Protein

processing

20� 75

60� 04

0� 008020

GO:0006289

Nucleotide-excisionrepair

20� 75

10

0� 07

0� 018049

GO:0007269

Neurotransm

ittersecretion

20� 75

13

0� 09

0� 027740

GO:0006897

Endocytosis

41� 5

63

0� 42

0� 030077

GO:0009615

Response

tovirus

20� 75

14

0� 09

0� 031342

GO:0000226

Microtubule

cytoskeletonorganizationandbiogenesis

20� 75

15

0� 1

0� 035116

GO:0007409

Axonogenesis

20� 75

16

0� 11

0� 039057

GO:0001756

Somitogenesis

20� 75

18

0� 12

0� 047408

GO:0045893

Positiveregulationoftranscription,DNA

dependent

20� 75

18

0� 12

0� 047408

Gonad,acute

exposure

GO:0006817

Phosphate

transport

52� 36

49

0� 33

0� 000912

GO:0006366

Transcriptionfrom

RNA

polymerase

II5

2� 36

57

0� 38

0� 001706

GO:0048511

Rhythmic

process

20� 94

30� 02

0� 001882

GO:0009072

Aromaticaminoacidfamilymetabolism

20� 94

50� 03

0� 003879

GO:0016126

Sterolbiosynthesis

20� 94

50� 03

0� 003879

GO:0019882

Antigen

presentation

20� 94

80� 05

0� 008086

GO:0008104

Protein

localization

20� 94

80� 05

0� 008086

GO:0006520

Aminoacidmetabolism

31� 42

29

0� 19

0� 009839

GO:0006334

Nucleosomeassem

bly

31� 42

29

0� 19

0� 009839

GO:0006694

Steroid

biosynthesis

20� 94

11

0� 07

0� 013637

GO:0007218

Neuropeptidesignallingpathway

31� 42

38

0� 25

0� 019303

GO:0000226

Microtubule


20� 94

15

0� 1

0� 022925

GO:0006461

Protein

complexassem

bly

31� 42

44

0� 29

0� 027640

GO:0043123

PositiveregulationofI-kappaBkinase/N

F-kappaBcascade

20� 94

20

0� 13

0� 037213

GO:0030036

Actin


31� 42

51

0� 34

0� 039414

GO:0001525

Angiogenesis

20� 94

21

0� 14

0� 040390


# 2008 The Authors


APPENDIX

II.Continued

GO

term

GO

definition

Number

altered†

Per

cent

altered

Number

unaltered

Per

cent

unaltered

P-value

GO:0009058

Biosynthesis

31� 42

52

0� 35

0� 041273

GO:0009653

Morphogenesis

20� 94

23

0� 15

0� 047037

Gonad,chronic

exposure

GO:0006957

Complementactivation,alternativepathway

21� 29

30� 02

0� 001012

GO:0007600

Sensory

perception

42� 58

40

0� 27

0� 001026

GO:0009618

Response

topathogenic

bacteria

21� 29

90� 06

0� 005345

GO:0030902

Hindbrain

development

21� 29

12

0� 08

0� 008668

GO:0051216

Cartilagedevelopment

21� 29

15

0� 1

0� 012698

GO:0007155

Celladhesion

74� 52

245

1� 63

0� 014808

GO:0045087

Innate

immuneresponse

21� 29

20

0� 13

0� 020864

GO:0006935

Chem

otaxis

21� 29

29

0� 19

0� 039576

GO:0001501

Skeletaldevelopment

21� 29

31

0� 21

0� 044352

*P<

0� 05.

†GO

categories

containingonly

onealtered

genewereexcluded

from

theanalysis.


# 2008 The Authors


Use of a 15 k gene microarray to determine gene expression changes in response to acute and chronic...

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