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E-GEOD-8251

Title: Transcriptional profiling of rat liver after drug treatment [original title: Non-genotoxic Hepatocarcinogens]
Organism(s): Rattus norvegicus
Description: 990 samples. 147 different compounds. [original description: There is no accurate and well-validated short-term test for non-genotoxic carcinogens, necessitating an expensive two year rodent bioassay before a risk assessment can begin. We have developed a short-term in vivo rat assay that predicts whether non-genotoxic chemicals are likely to induce hepatic tumors based on transcript profiles in the liver. Using a large independent test set, assay accuracy was found to be superior to existing pathological and genomic markers. Comparison of the test chemical's signature profile to reference carcinogens of known mechanism can also identify a potential mode(s) of action, allowing an early assessment of human cancer risk. Guidelines for commercial use: http://www.iconixbiosciences.com/guidelineCommUse.pdf Keywords: dose response, time course, compound treatment Treatment of male Sprague-Dawley rats with 147 non-genotoxic compounds at various doses and durations, in biological triplicate, along with vehicle-matched control animals. Liver samples were assayed for gene expression. Hepatocarcinogenic and non-carcinogenic compounds were included. A classifier for carcinogenicity was built on a training set of 25 carcinogens and 75 noncarcinogens (randomly selected compounds, maximum tolerated dose, 5 day timepoints), and tested on the remaining 47 compounds at various timepoints. A total of 990 samples were hybridized to single-channel CodeLink RU1 arrays. Biological triplicates were combined with matched control samples to calculate log ratios.]
Design(s): transcription profiling by array
Experimental factor(s):
experiment date
138 recorded
12/11/2001 11-DEC-2001 04-DEC-2001 12/4/2001 13-NOV-2001 11/13/2001 5/13/2002 13-MAY-2002 27-NOV-2001 11/27/2001 5/20/2002 20-MAY-2002 7/8/2002 08-JUL-2002 25-APR-2003 4/25/2003 1/22/2002 22-JAN-2002 22-OCT-2002 10/22/2002 3/25/2002 25-MAR-2002 08-APR-2002 4/8/2002 16-OCT-2001 10/16/2001 10/30/2001 30-OCT-2001 8/19/2002 19-AUG-2002 10/14/2003 14-OCT-2003 9/16/2002 16-SEP-2002 29-APR-2002 4/29/2002 6/17/2002 17-JUN-2002 10/7/2002 07-OCT-2002 15-APR-2002 4/15/2002 05-FEB-2002 2/5/2002 22-JUL-2002 7/22/2002 09-OCT-2001 10/9/2001 08-JAN-2002 1/8/2002 02-OCT-2001 10/2/2001 20-MAY-2004 5/20/2004 11-FEB-2002 2/11/2002 01-APR-2002 4/1/2002 11/6/2001 06-NOV-2001 9/16/2003 16-SEP-2003 14-OCT-2002 10/14/2002 9/24/2001 24-SEP-2001 10/21/2002 21-OCT-2002 8/13/2002 13-AUG-2002 9/9/2002 09-SEP-2002 11-MAR-2004 3/11/2004 4/9/2003 09-APR-2003 20-JAN-2003 1/20/2003 27-MAY-2004 5/27/2004 5/6/2002 06-MAY-2002 9/30/2002 30-SEP-2002 23-OCT-2001 10/23/2001 7/29/2002 29-JUL-2002 4/22/2002 22-APR-2002 4/8/2003 08-APR-2003 1/15/2002 15-JAN-2002 18-FEB-2003 2/18/2003 28-OCT-2002 10/28/2002 17-FEB-2004 2/17/2004 24-JUN-2002 6/24/2002 08-OCT-2002 10/8/2002 7/15/2002 15-JUL-2002 03-MAY-2004 5/3/2004 03-SEP-2004 9/3/2004 18-MAR-2002 3/18/2002 16-JUL-2002 7/16/2002 9/23/2002 23-SEP-2002 7/29/2004 29-JUL-2004 3/11/2002 11-MAR-2002 7/30/2002 30-JUL-2002 7/12/2004 12-JUL-2004 14-MAY-2002 5/14/2002 10-JUN-2002 6/10/2002 8/5/2002 05-AUG-2002 7/22/2004 22-JUL-2004 9/10/2002 10-SEP-2002 9/2/2003 02-SEP-2003 9/24/2002 24-SEP-2002
treatment duration
11 recorded
5 days 3 days 1 days .25 days 7 days 91 days 6 days 4 days 30 days 0 days 28 days
treatment compound
149 recorded
ethylene glycol none NA progesterone OXFENDAZOLE SPIRONOLACTONE CLOMIPRAMINE FLUVASTATIN OXYMETHOLONE CHOLINE CHLORIDE GERANIOL CYPROTERONE ACETATE rosiglitazone rofecoxib ERYTHROMYCIN benzoic acid MIFEPRISTONE diazepam PRIMIDONE TOCAINIDE 1,1-DICHLOROETHENE PRAVASTATIN cyclosporin A AMOXAPINE quetiapine clofibric acid ZIDOVUDINE cytarabine simvastatin diethylstilbestrol LEAD(IV) ACETATE CARBIMAZOLE citalopram MEGESTROL ACETATE PROPYLTHIOURACIL OXYQUINOLINE VINORELBINE ALFACALCIDOL phenobarbital THIOACETAMIDE carbon tetrachloride CHOLECALCIFEROL azithromycin carbamazepine CLARITHROMYCIN ethanol atorvastatin TOLAZAMIDE ACETAMINOPHEN CERIVASTATIN 17-METHYLTESTOSTERONE AMLODIPINE MELOXICAM NORETHINDRONE ACETATE RABEPRAZOLE PERGOLIDE fluconazole BETA-NAPHTHOFLAVONE VENLAFAXINE CHLOROFORM methapyrilene FENBENDAZOLE LIPOPOLYSACCHARIDE E. COLI O55_B5 N,N-DIMETHYLFORMAMIDE BEZAFIBRATE STANOZOLOL NORETHINDRONE cycloheximide CITRIC ACID CLOMIPHENE bisphenol A ALLYL ALCOHOL 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN raloxifene PRAZIQUANTEL prednisolone olanzapine DICHLORVOS OMEPRAZOLE IBUPROFEN FINASTERIDE CORTISONE PROPYLENE GLYCOL troglitazone ETHYLESTRENOL LOVASTATIN PHENACETIN LEVAMISOLE ciprofloxacin TRICHLOROACETIC ACID BIS(2-ETHYLHEXYL)PHTHALATE testosterone PERHEXILINE CARVEDILOL nevirapine ISOPRENALINE diclofenac indomethacin PEMOLINE PENTOBARBITAL HYDROCORTISONE fenofibrate PYRAZINAMIDE GLIPIZIDE etoposide valproic acid SILDENAFIL PHENOTHIAZINE pirinixic acid ETHISTERONE LORAZEPAM SPARFLOXACIN TRETINOIN PROMETHAZINE BENZETHONIUM CHLORIDE SAFROLE GEMFIBROZIL METHYLDOPA pioglitazone HEXACHLOROPHENE celecoxib tetracycline fluoxetine ticlopidine clotrimazole ERGOCALCIFEROL GLIMEPIRIDE ESTRIOL isotretinoin ASPIRIN VINBLASTINE ITRACONAZOLE ROXITHROMYCIN BUPROPION clofibrate BETA-ESTRADIOL acyclovir CATECHOL KETOROLAC KETOCONAZOLE GENTIAN VIOLET anastrozole azathioprine FAMCICLOVIR NAFENOPIN RIFABUTIN NISOLDIPINE ETHINYLESTRADIOL ETODOLAC
solvent
8 recorded
water CORN OIL CMC saline POLYSORBATE 80 UNKNOWN PEG400 UNTREATED
dose
108 recorded
3525 mg/kg NA 164 mg/kg 1500 mg/kg 300 mg/kg 115 mg/kg 94 mg/kg 1170 mg/kg 2550 mg/kg 2500 mg/kg 1800 mg/kg 1550 mg/kg 1700 mg/kg 710 mg/kg 750 mg/kg 224 mg/kg 600 mg/kg 1200 mg/kg 350 mg/kg 313 mg/kg 500 mg/kg 448 mg/kg 1540 mg/kg 487 mg/kg 280 mg/kg 400 mg/kg 90 mg/kg 132 mg/kg 625 mg/kg 68 mg/kg 1.5 mg/kg .043 mg/kg 80 mg/kg 200 mg/kg 1175 mg/kg 8 mg/kg 225 mg/kg 490 mg/kg 476 mg/kg 6000 mg/kg 972 mg/kg 7 mg/kg 2000 mg/kg 19 mg/kg 33 mg/kg 125 mg/kg 1024 mg/kg 1.1 mg/kg 394 mg/kg 320 mg/kg 100 mg/kg 375 mg/kg 1.25 mg/kg 1400 mg/kg 617 mg/kg 150 mg/kg .25 mg/kg 3000 mg/kg 250 mg/kg 610 mg/kg 32 mg/kg .02 mg/kg 650 mg/kg 184 mg/kg 23 mg/kg 17 mg/kg 415 mg/kg 263 mg/kg 800 mg/kg 206 mg/kg 390 mg/kg 619 mg/kg 120 mg/kg 450 mg/kg 474 mg/kg 1000 mg/kg 15 mg/kg 10 mg/kg 12 mg/kg 70 mg/kg 56 mg/kg 215 mg/kg 188 mg/kg 420 mg/kg 386 mg/kg 364 mg/kg 113 mg/kg 30 mg/kg 488 mg/kg 700 mg/kg 325 mg/kg 52 mg/kg 223 mg/kg 178 mg/kg .3 mg/kg 1093 mg/kg 312 mg/kg 895 mg/kg 980 mg/kg 195 mg/kg 48 mg/kg 227 mg/kg 18 mg/kg 54 mg/kg 338 mg/kg 1125 mg/kg 1480 mg/kg 24 mg/kg
administration route
5 recorded
ORAL GAVAGE SUBCUTANEOUS INTRAVENOUS INTRAPERITONEAL NONE
Publication(s): Fielden MR, Brennan R, Gollub J
A gene expression biomarker provides early prediction and mechanistic assessment of hepatic tumor induction by nongenotoxic chemicals. PubMed:17557906

Sample attribute(s):
Material Type
1 recorded
polyA RNA
sex
1 recorded
Male
experiment date
69 recorded
12/11/2001 12/4/2001 11/13/2001 5/13/2002 11/27/2001 5/20/2002 7/8/2002 4/25/2003 1/22/2002 10/22/2002 3/25/2002 4/8/2002 10/16/2001 10/30/2001 8/19/2002 10/14/2003 9/16/2002 4/29/2002 6/17/2002 10/7/2002 4/15/2002 2/5/2002 7/22/2002 10/9/2001 1/8/2002 10/2/2001 5/20/2004 2/11/2002 4/1/2002 11/6/2001 9/16/2003 10/14/2002 9/24/2001 10/21/2002 8/13/2002 9/9/2002 3/11/2004 4/9/2003 1/20/2003 5/27/2004 5/6/2002 9/30/2002 10/23/2001 7/29/2002 4/22/2002 4/8/2003 1/15/2002 2/18/2003 10/28/2002 2/17/2004 6/24/2002 10/8/2002 7/15/2002 5/3/2004 9/3/2004 3/18/2002 7/16/2002 9/23/2002 7/29/2004 3/11/2002 7/30/2002 7/12/2004 5/14/2002 6/10/2002 8/5/2002 7/22/2004 9/10/2002 9/2/2003 9/24/2002
solvent
8 recorded
water CORN OIL CMC (0.5% carboxymethylcellulose) saline POLYSORBATE 80 UNKNOWN PEG400 UNTREATED
dose
108 recorded
3525 mg/kg 0 mg/kg 164 mg/kg 1500 mg/kg 300 mg/kg 115 mg/kg 94 mg/kg 1170 mg/kg 2550 mg/kg 2500 mg/kg 1800 mg/kg 1550 mg/kg 1700 mg/kg 710 mg/kg 750 mg/kg 224 mg/kg 600 mg/kg 1200 mg/kg 350 mg/kg 313 mg/kg 500 mg/kg 448 mg/kg 1540 mg/kg 487 mg/kg 280 mg/kg 400 mg/kg 90 mg/kg 132 mg/kg 625 mg/kg 68 mg/kg 1.5 mg/kg 0.043 mg/kg 80 mg/kg 200 mg/kg 1175 mg/kg 8 mg/kg 225 mg/kg 490 mg/kg 476 mg/kg 6000 mg/kg 972 mg/kg 7 mg/kg 2000 mg/kg 19 mg/kg 33 mg/kg 125 mg/kg 1024 mg/kg 1.1 mg/kg 394 mg/kg 320 mg/kg 100 mg/kg 375 mg/kg 1.25 mg/kg 1400 mg/kg 617 mg/kg 150 mg/kg 0.25 mg/kg 3000 mg/kg 250 mg/kg 610 mg/kg 32 mg/kg 0.02 mg/kg 650 mg/kg 184 mg/kg 23 mg/kg 17 mg/kg 415 mg/kg 263 mg/kg 800 mg/kg 206 mg/kg 390 mg/kg 619 mg/kg 120 mg/kg 450 mg/kg 474 mg/kg 1000 mg/kg 15 mg/kg 10 mg/kg 12 mg/kg 70 mg/kg 56 mg/kg 215 mg/kg 188 mg/kg 420 mg/kg 386 mg/kg 364 mg/kg 113 mg/kg 30 mg/kg 488 mg/kg 700 mg/kg 325 mg/kg 52 mg/kg 223 mg/kg 178 mg/kg 0.3 mg/kg 1093 mg/kg 312 mg/kg 895 mg/kg 980 mg/kg 195 mg/kg 48 mg/kg 227 mg/kg 18 mg/kg 54 mg/kg 338 mg/kg 1125 mg/kg 1480 mg/kg 24 mg/kg
administration route
5 recorded
gavage subcutaneous injection intravenous injection intraperitoneal injection NONE
treatment duration
11 recorded
5 days 3 days 1 days .25 days 7 days 91 days 6 days 4 days 30 days 0 days 28 days
treatment compound
148 recorded
ethylene glycol vehicle control condition progesterone oxfendazole spironolactone clomipramine fluvastatin OXYMETHOLONE CHEMBL1200585 choline chloride geraniol cyproterone acetate rosiglitazone rofecoxib erythromycin benzoic acid mifepristone diazepam primidone tocainide 1,1-dichloroethene pravastatin cyclosporin A amoxapine quetiapine clofibric acid zidovudine cytarabine simvastatin diethylstilbestrol LEAD(IV) ACETATE CHEMBL1909063 carbimazole citalopram megestrol acetate 6-propyl-2-thiouracil quinolin-8-ol vinorelbine ALFACALCIDOL CHEMBL1601669 phenobarbital thioacetamide tetrachloromethane calciol azithromycin carbamazepine clarithromycin ethanol atorvastatin TOLAZAMIDE CHEMBL817 paracetamol cerivastatin methyltestosterone amlodipine MELOXICAM NORETHINDRONE ACETATE CHEMBL1201146 rabeprazole pergolide fluconazole BETA-NAPHTHOFLAVONE CHEMBL26260 venlafaxine chloroform methapyrilene FENBENDAZOLE CHEMBL37161 lipopolysaccharide N,N-dimethylformamide bezafibrate STANOZOLOL CHEMBL1200324 norethisterone cycloheximide citric acid clomiphene bisphenol A allyl alcohol 2,3,7,8-tetrachlorodibenzodioxine raloxifene praziquantel prednisolone olanzapine dichlorvos omeprazole ibuprofen finasteride cortisone propane-1,2-diol troglitazone ETHYLESTRENOL CHEMBL1200623 lovastatin phenacetin LEVAMISOLE CHEMBL1454 ciprofloxacin trichloroacetic acid bis(2-ethylhexyl) phthalate testosterone perhexiline carvedilol nevirapine isoprenaline diclofenac indomethacin PEMOLINE CHEMBL1177 pentobarbital cortisol fenofibrate pyrazinecarboxamide GLIPIZIDE CHEMBL1073 etoposide valproic acid sildenafil phenothiazine pirinixic acid ETHISTERONE CHEMBL241694 lormetazepam sparfloxacin all-trans-retinoic acid promethazine BENZETHONIUM CHLORIDE CHEMBL221753 SAFROLE gemfibrozil alpha-methyl-L-dopa pioglitazone HEXACHLOROPHENE CHEMBL496 celecoxib tetracycline fluoxetine ticlopidine clotrimazole vitamin D2 glimepiride estriol isotretinoin acetylsalicylic acid vincaleukoblastine itraconazole roxithromycin bupropion clofibrate 17beta-estradiol acyclovir catechol KETOROLAC ketoconazole GENTIAN VIOLET CHEMBL64894 anastrozole azathioprine famciclovir NAFENOPIN PubChem 19592 rifabutin NISOLDIPINE CHEMBL1726 17alpha-ethynylestradiol etodolac
age
1 recorded
6 to 8 weeks
frequency of dosing
1 recorded
DAILY
organism part
1 recorded
liver
Label
1 recorded
biotin
Organism
1 recorded
Rattus norvegicus
Contact(s): Jeremy GollubRichard BrennanJeremy GollubMark Fielden
Release Date: 6/22/2007
Submission Date:
Metadata Downloads Download Study Metadata as ISAtabDownload Study Metadata as ISAtab
Assay Downloads
transcription profiling using DNA microarray
990 assays