{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:57:07Z","timestamp":1791205027776,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,8]]},"DOI":"10.1093\/toxsci\/kfq118","type":"journal-article","created":{"date-parts":[[2010,4,20]],"date-time":"2010-04-20T02:59:35Z","timestamp":1271732375000},"page":"452-466","source":"Crossref","is-referenced-by-count":146,"title":["Human Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR) Support the Hypertrophic but not the Hyperplastic Response to the Murine Nongenotoxic Hepatocarcinogens Phenobarbital and Chlordane In Vivo"],"prefix":"10.1093","volume":"116","author":[{"given":"Jillian","family":"Ross","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon M.","family":"Plummer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Rode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Scheer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conrad C.","family":"Bower","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ortwin","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin J.","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Roland","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford R.","family":"Elcombe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,4,19]]},"reference":[{"key":"key\n\t\t\t\t20170508183430_bib1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S0022-3476(80)80123-5","article-title":"The effects of phenobarbital and diphenylhydantoin on liver function and morphology","volume":"97","year":"1980","journal-title":"J. Pediatr."},{"key":"key\n\t\t\t\t20170508183430_bib2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/01926230490440934","article-title":"Prediction of rodent carcinogenesis: an evaluation of prechronic liver lesions as forecasters of liver tumors in NTP carcinogenicity studies","volume":"32","year":"2004","journal-title":"Toxicol. Pathol."},{"key":"key\n\t\t\t\t20170508183430_bib3","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1177\/096032719401300201","article-title":"Mechanistically based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis","volume":"13","year":"1994","journal-title":"Hum. Exp. Toxicol."},{"key":"key\n\t\t\t\t20170508183430_bib4","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.1093\/nar\/gkg419","article-title":"Alternatively spliced isoforms of the human constitutive androstane receptor","volume":"31","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170508183430_bib5","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1124\/mol.105.013417","article-title":"Retinoid X receptor-alpha-dependent transactivation by a naturally occurring structural variant of human constitutive androstane receptor (NR1I3)","volume":"68","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"key\n\t\t\t\t20170508183430_bib6","first-page":"219","article-title":"Cell proliferation in the liver and thyroid of C57Bl\/10J mice after dietary administration of chlordane","volume":"101","year":"1993","journal-title":"Environ. Health Perspect."},{"key":"key\n\t\t\t\t20170508183430_bib7","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/0278-6915(93)90225-N","article-title":"Hepatic peroxisome proliferation in rodents and its significance for humans","volume":"31","year":"1993","journal-title":"Food Chem. Toxicol."},{"key":"key\n\t\t\t\t20170508183430_bib8","first-page":"1199","article-title":"The significance of mouse liver tumour formation for carcinogenic risk assessment: results and conclusions from a survey of ten years of testing by the agrochemical industry","volume":"105","year":"1997","journal-title":"Environ. Health Perspect."},{"key":"key\n\t\t\t\t20170508183430_bib9","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.1158\/0008-5472.CAN-04-0322","article-title":"Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha","volume":"64","year":"2004","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170508183430_bib10","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1124\/mol.108.053702","article-title":"Di(2-ethylhexyl) phthalate is a highly potent agonist for the human constitutive androstane receptor splice variant HCAR2","volume":"75","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"key\n\t\t\t\t20170508183430_bib11","author":"ECETOC Monograph","year":"1982","journal-title":"Hepatocarcinogenesis in laboratory rodents: relevance for man"},{"key":"key\n\t\t\t\t20170508183430_bib12","article-title":"Liver mRNA and miRNA profiling of phenobarbital (PB)-treated PXR\/CAR double knock-out and humanized mice provides insight into mechanism(s) of PB-mediated mouse hepatocarcinogenesis","year":"2010"},{"key":"key\n\t\t\t\t20170508183430_bib13","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1124\/dmd.32.3.340","article-title":"Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression","volume":"32","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"key\n\t\t\t\t20170508183430_bib14","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1146\/annurev.pa.31.040191.001345","article-title":"Role of persistent, non-genotoxic tissue damage in rodent cancer and relevance to humans","volume":"31","year":"1991","journal-title":"Ann. Rev. Pharmacol. Toxicol."},{"key":"key\n\t\t\t\t20170508183430_bib16","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.tox.2009.01.007","article-title":"Comparison of the effects of the synthetic pyrethroid Metofluthrin and phenobarbital on CYP2B form induction and replicative DNA synthesis in cultured rat and human hepatocytes","volume":"258","year":"2009","journal-title":"Toxicology"},{"key":"key\n\t\t\t\t20170508183430_bib17","first-page":"51","article-title":"Mode of action in relevance of rodent liver tumors to human cancer risk","volume":"9","year":"2006","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170508183430_bib18","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1210\/me.2004-0520","article-title":"Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor","volume":"19","year":"2005","journal-title":"Mol. Endocrinol."},{"key":"key\n\t\t\t\t20170508183430_bib19","volume-title":"IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Thyrotropic Agents","author":"International Agency for Research on Cancer (IARC)","year":"2001"},{"key":"key\n\t\t\t\t20170508183430_bib20","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1124\/mol.65.3.496","article-title":"Identification of novel alternative splice variants of human constitutive androstane receptor and characterization of their expression in the liver","volume":"65","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"key\n\t\t\t\t20170508183430_bib21","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.fct.2009.03.014","article-title":"Effect of chronic phenobarbitone administration on liver tumour formation in the C57BL\/10J mouse","volume":"47","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"key\n\t\t\t\t20170508183430_bib22","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1080\/00498250903098184","article-title":"Species differences in the hepatic effects of inducers of CYP2B and CYP4A subfamily forms: relationship to rodent liver tumour formation","volume":"39","year":"2009","journal-title":"Xenobiotica"},{"key":"key\n\t\t\t\t20170508183430_bib23","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1124\/jpet.104.069310","article-title":"Expression of constitutive androstane receptor splice variants in human tissues and their functional consequences","volume":"311","year":"2004","journal-title":"J. Pharmacol. Exp. Therap."},{"key":"key\n\t\t\t\t20170508183430_bib24","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1128\/MCB.15.6.3012","article-title":"Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators","volume":"15","year":"1995","journal-title":"Mol. Cell Biol."},{"key":"key\n\t\t\t\t20170508183430_bib25","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","year":"1951","journal-title":"J. Biol. Chem."},{"key":"key\n\t\t\t\t20170508183430_bib26","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1093\/carcin\/16.11.2617","article-title":"Hepatocarcinogenicity of chlordane in B6C3F1 and B6D2F1 male mice: evidence for regression in B6C3F1 mice and carcinogenesis independent of ras proto-oncogene activation","volume":"16","year":"1995","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20170508183430_bib27","first-page":"345","article-title":"Mouse liver tumours and microsomal enzyme-inducing drugs:experimental and clinical perspectives with phenobarbital","volume-title":"Mouse Liver Carcinogenesis: Mechanisms and Species Comparisons","year":"1990"},{"key":"key\n\t\t\t\t20170508183430_bib28","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1093\/carcin\/bgi329","article-title":"Differential susceptibility of mice humanized for peroxisome proliferator-activated receptor alpha to Wy-14,643-induced liver tumorigenesis","volume":"27","year":"2006","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20170508183430_bib29","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/jnci\/81.10.803","article-title":"Cancer among epileptic patients exposed to anticonvulsant drugs","volume":"81","year":"1989","journal-title":"J. Natl. Cancer Inst."},{"key":"key\n\t\t\t\t20170508183430_bib30","first-page":"294","article-title":"Antiepileptic treatment and risk for hepatobiliary cancer and malignant lymphoma","volume":"55","year":"1995","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170508183430_bib31","first-page":"1143","article-title":"Testing for induction of DNA synthesis in human hepatocyte primary cultures by rat liver tumor promoters","volume":"51","year":"1991","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170508183430_bib32","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1093\/carcin\/18.11.2029","article-title":"Role of PPARalpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643","volume":"18","year":"1997","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20170508183430_bib33","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1365-2125.1978.tb04597.x","article-title":"Liver size and indices of drug metabolism in epileptics","volume":"6","year":"1978","journal-title":"Br. J. Clin. Pharmacol."},{"key":"key\n\t\t\t\t20170508183430_bib34","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/BF00542550","article-title":"Hepatic blood flow and drug metabolism in patients on enzyme-inducing anticonvulsants","volume":"22","year":"1982","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"key\n\t\t\t\t20170508183430_bib35","article-title":"In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice","year":"2010","journal-title":"Drug Metab. Dispos"},{"key":"key\n\t\t\t\t20170508183430_bib36","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1172\/JCI35483","article-title":"A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response","volume":"118","year":"2008","journal-title":"J. Clin. Invest."},{"key":"key\n\t\t\t\t20170508183430_bib38","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3109\/10408447409079856","article-title":"Induction of liver growth by xenobiotic compounds and other stimuli","volume":"3","year":"1974","journal-title":"Crit. Rev. Tox."},{"key":"key\n\t\t\t\t20170508183430_bib39","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0009-2797(80)90017-4","article-title":"Adaptive responses of rat liver to the gestagen and anti-androgen cyproterone acetate and other inducers II: Induction of growth","volume":"31","year":"1980","journal-title":"Chem. Biol. Interact."},{"key":"key\n\t\t\t\t20170508183430_bib40","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.1128\/MCB.00317-07","article-title":"Peroxisome proliferator-activated receptor alpha regulates a microRNA-mediated signaling cascade responsible for hepatocellular proliferation","volume":"27","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"key\n\t\t\t\t20170508183430_bib41","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1080\/00498250600861827","article-title":"Nuclear receptors CAR and PXR in the regulation of hepatic metabolism","volume":"36","year":"2006","journal-title":"Xenobiotica"},{"key":"key\n\t\t\t\t20170508183430_bib42","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1038\/35038112","article-title":"The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism","volume":"407","year":"2000","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170508183430_bib43","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0163-7258(96)00067-8","article-title":"Phenobarbital mechanistic data and risk assessment: enzyme induction, enhanced cell proliferation, and tumor promotion","volume":"71","year":"1996","journal-title":"Pharm. Ther."},{"key":"key\n\t\t\t\t20170508183430_bib44","doi-asserted-by":"crossref","first-page":"7197","DOI":"10.1158\/0008-5472.CAN-04-1459","article-title":"The orphan nuclear receptor constitutive active\/androstane receptor is essential for liver tumor promotion by phenobarbital in mice","volume":"64","year":"2004","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170508183430_bib45","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1093\/toxsci\/kfm206","article-title":"The PPAR alpha humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha","volume":"101","year":"2008","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170508183430_bib46","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1039\/9781847558428-00417","article-title":"Receptor mediated regulation of cytochromes P450","volume-title":"Cytochromes P450: Role in the Metabolism and Toxicity of Drugs and Other Xenobiotics","year":"2008"}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/116\/2\/452\/16681412\/kfq118.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T09:24:56Z","timestamp":1635240296000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article-lookup\/doi\/10.1093\/toxsci\/kfq118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,19]]},"references-count":44,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2010,4,19]]},"published-print":{"date-parts":[[2010,8]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfq118","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,19]]}}}