{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:25:40Z","timestamp":1790702740837,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,3]]},"DOI":"10.1093\/toxsci\/kfl188","type":"journal-article","created":{"date-parts":[[2006,12,17]],"date-time":"2006-12-17T01:25:10Z","timestamp":1166318710000},"page":"72-82","source":"Crossref","is-referenced-by-count":43,"title":["Orphan Nuclear Receptor Constitutive Active\/Androstane Receptor\u2013Mediated Alterations in DNA Methylation during Phenobarbital Promotion of Liver Tumorigenesis"],"prefix":"10.1093","volume":"96","author":[{"given":"Jennifer M.","family":"Phillips","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Negishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Maronpot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay I.","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,12,16]]},"reference":[{"key":"key\n\t\t\t\t20170607121909_bib1","doi-asserted-by":"crossref","first-page":"22250","DOI":"10.1074\/jbc.M314111200","article-title":"Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice","volume":"21","author":"Assem","year":"2004","journal-title":"J. Biol. Chem."},{"key":"key\n\t\t\t\t20170607121909_bib2","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/toxsci\/kfj179","article-title":"Altered methylation in gene-specific and GC-rich regions of DNA is progressive and nonrandom during promotion of skin tumorigenesis","volume":"91","author":"Bachman","year":"2006","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170607121909_bib3","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/toxsci\/kfj155","article-title":"Phenobarbital induces progressive patterns of GC-rich and gene-specific altered DNA methylation in the liver of tumor-prone B6C3F1 mice","volume":"91","author":"Bachman","year":"2006","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170607121909_bib4","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1128\/MCB.14.3.1544","article-title":"A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements","volume":"14","author":"Baes","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"key\n\t\t\t\t20170607121909_bib5","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/17533","article-title":"A mammalian protein with specific demethylase activity for mCpG DNA","volume":"397","author":"Bhattacharya","year":"1999","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170607121909_bib6","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1073\/pnas.88.3.911","article-title":"Mutational activation of the c-Ha-ras gene in liver tumors of different rodent strains: Correlation with susceptibility to hepatocarcinogenesis","volume":"88","author":"Buchmann","year":"1991","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"key\n\t\t\t\t20170607121909_bib7","doi-asserted-by":"crossref","first-page":"23565","DOI":"10.1074\/jbc.272.38.23565","article-title":"Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR","volume":"272","author":"Choi","year":"1997","journal-title":"J. Biol. Chem."},{"key":"key\n\t\t\t\t20170607121909_bib8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/ng0595-20","article-title":"CpNpG methylation in mammalian cells","volume":"10","author":"Clark","year":"1995","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20170607121909_bib9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0092-8674(95)90228-7","article-title":"Alterations in DNA methylation may play a variety of roles in carcinogenesis","volume":"83","author":"Counts","year":"1995","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170607121909_bib10","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1093\/carcin\/17.6.1251","article-title":"Cell proliferation and global methylation status changes in mouse liver after phenobarbital and\/or choline-devoid, methionine-deficient diet administration","volume":"17","author":"Counts","year":"1996","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20170607121909_bib11","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3181\/00379727-202-43511C","article-title":"The initiation promotion-progression model of rat hepatocarcinogenesis","volume":"202","author":"Dragan","year":"1993","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"key\n\t\t\t\t20170607121909_bib12","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1126\/science.1083557","article-title":"Chromosomal instability and tumors promoted by DNA hypomethylation","volume":"300","author":"Eden","year":"2003","journal-title":"Science"},{"key":"key\n\t\t\t\t20170607121909_bib13","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1093\/nar\/10.8.2709","article-title":"Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells","volume":"10","author":"Ehrlich","year":"1982","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170607121909_bib14","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nrg1349","article-title":"Epigenomics: Beyond CpG islands","volume":"5","author":"Fazzari","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"key\n\t\t\t\t20170607121909_bib15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrg1748","article-title":"The epigenetic progenitor origin of human cancer","volume":"7","author":"Feinberg","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"key\n\t\t\t\t20170607121909_bib16","doi-asserted-by":"crossref","first-page":"6883","DOI":"10.1093\/nar\/11.19.6883","article-title":"The 5-methylcytosine content of DNA from human tumors","volume":"11","author":"Gama-Sosa","year":"1983","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170607121909_bib17","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1126\/science.1083558","article-title":"Induction of tumors in mice by genomic hypomethylation","volume":"300","author":"Gaudet","year":"2003","journal-title":"Science"},{"key":"key\n\t\t\t\t20170607121909_bib18","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/carcin\/5.10.1367","article-title":"The induction of liver cancer by dietary deficiency of choline and methionine without added carcinogens","volume":"5","author":"Ghoshal","year":"1984","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20170607121909_bib19","first-page":"594","article-title":"Identification and characterization of differentially methylated regions of genomic DNA by methylation-sensitive arbitrarily primed PCR","volume":"57","author":"Gonzalgo","year":"1997","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170607121909_bib20","first-page":"97","article-title":"Recent advances in cancer research: Mouse models of tumorigenesis","volume":"1602","author":"Herzig","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"key\n\t\t\t\t20170607121909_bib21","doi-asserted-by":"crossref","first-page":"5652","DOI":"10.1128\/MCB.18.10.5652","article-title":"The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene","volume":"18","author":"Honkakoski","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"key\n\t\t\t\t20170607121909_bib22","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","author":"Huang","year":"2005","journal-title":"Mol. Endocrinol."},{"key":"key\n\t\t\t\t20170607121909_bib23","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/5947","article-title":"Cancer epigenetics comes of age","volume":"21","author":"Jones","year":"1999","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t20170607121909_bib24","doi-asserted-by":"crossref","first-page":"4452","DOI":"10.1093\/nar\/29.21.4452","article-title":"5-Methylcytosine DNA glycosylase participates in the genome-wide loss of DNA methylation occurring during mouse myoblast differentiation","volume":"29","author":"Jost","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t20170607121909_bib25","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1074\/jbc.M109326200","article-title":"Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor","volume":"25","author":"Kast","year":"2002","journal-title":"J. Biol. Chem."},{"key":"key\n\t\t\t\t20170607121909_bib26","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1210\/mend.14.11.0547","article-title":"Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene","volume":"14","author":"Kawamoto","year":"2000","journal-title":"Mol. Endocrinol."},{"key":"key\n\t\t\t\t20170607121909_bib27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/03602530600569851","article-title":"Phenobarbital confers its diverse effects by activating the orphan nuclear receptor CAR","volume":"38","author":"Kodama","year":"2006","journal-title":"Drug Metab. Rev."},{"key":"key\n\t\t\t\t20170607121909_bib28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00228-002-0429-6","article-title":"Cancer incidence among patients using antiepileptic drugs: A long-term follow-up of 28,000 patients","volume":"58","author":"Lamminp\u00e4\u00e4","year":"2002","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"key\n\t\t\t\t20170607121909_bib29","doi-asserted-by":"crossref","first-page":"17277","DOI":"10.1074\/jbc.M300138200","article-title":"Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes","volume":"278","author":"Maglich","year":"2003","journal-title":"J. Biol. Chem."},{"key":"key\n\t\t\t\t20170607121909_bib30","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.2174\/1568026033451709","article-title":"Orphan nuclear receptor modulators","volume":"3","author":"Mohan","year":"2003","journal-title":"Curr. Top. Med. Chem."},{"key":"key\n\t\t\t\t20170607121909_bib31","doi-asserted-by":"crossref","first-page":"15122","DOI":"10.1074\/jbc.M001215200","article-title":"Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands","volume":"275","author":"Moore","year":"2000","journal-title":"J. Biol. Chem."},{"key":"key\n\t\t\t\t20170607121909_bib32","doi-asserted-by":"crossref","first-page":"52353","DOI":"10.1074\/jbc.M407695200","article-title":"Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: Implications for epigenetic reprogramming","volume":"279","author":"Morgan","year":"2004","journal-title":"J. Biol. Chem."},{"key":"key\n\t\t\t\t20170607121909_bib33","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1158\/0008-5472.CAN-04-3340","article-title":"Discovery of aberrant expression of R-RAS by cancer-linked DNA hypomethylation in gastric cancer using microarrays","volume":"65","author":"Nishigaki","year":"2005","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170607121909_bib34","first-page":"1663","article-title":"Promoter methylation of cyclin D2 gene in gastric carcinoma","volume":"23","author":"Oshimo","year":"2003","journal-title":"Int. J. Oncol."},{"key":"key\n\t\t\t\t20170607121909_bib35","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1146\/annurev.pa.30.040190.002341","article-title":"Altered hepatic foci: Their role in murine hepatocarcinogenesis","volume":"30","author":"Pitot","year":"1990","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"key\n\t\t\t\t20170607121909_bib36","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/nrc1235","article-title":"Opinion: Comparative biology of mouse versus human cells: Modelling human cancer in mice","volume":"3","author":"Rangarajan","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"key\n\t\t\t\t20170607121909_bib37","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.bbrc.2006.04.007","article-title":"The orphan nuclear receptor GCNF recruits DNA methyltransferase for Oct-3\/4 silencing","volume":"344","author":"Sato","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"key\n\t\t\t\t20170607121909_bib38","first-page":"5127","article-title":"DNA synthesis, apoptosis, and phenotypic expression as determinants of growth of altered foci in rat liver during phenobarbital promotion","volume":"50","author":"Schulte-Hermann","year":"1990","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170607121909_bib39","doi-asserted-by":"crossref","first-page":"4229","DOI":"10.1073\/pnas.92.10.4229","article-title":"Preferential isolation of DNA fragments associated with CpG islands","volume":"92","author":"Shiraishi","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"key\n\t\t\t\t20170607121909_bib40","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1210\/me.2003-0397","article-title":"CAR, driving into the future","volume":"18","author":"Swales","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"key\n\t\t\t\t20170607121909_bib41","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1128\/MCB.20.9.2951-2958.2000","article-title":"The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR","volume":"20","author":"Tzameli","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"key\n\t\t\t\t20170607121909_bib42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/mol.61.1.1","article-title":"Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital","volume":"61","author":"Ueda","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"key\n\t\t\t\t20170607121909_bib43","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1124\/mol.61.6.1284","article-title":"Residue threonine 350 confers steroid hormone responsiveness to the mouse nuclear orphan receptor CAR","volume":"61","author":"Ueda","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"key\n\t\t\t\t20170607121909_bib44","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/toxsci\/68.1.51","article-title":"Effects of phenobarbital on DNA methylation in GC-rich regions of hepatic DNA from mice that exhibit different levels of susceptibility to liver tumorigenesis","volume":"68","author":"Watson","year":"2002","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170607121909_bib45","first-page":"53","article-title":"Phenobarbital mechanistic data and risk assessment: Enzyme induction, enhanced cell proliferation, and tumor promotion","volume":"71","author":"Whysner","year":"1996","journal-title":"Pharmacol. Ther."},{"key":"key\n\t\t\t\t20170607121909_bib46","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","author":"Yamamoto","year":"2004","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170607121909_bib47","doi-asserted-by":"crossref","first-page":"4157","DOI":"10.1093\/nar\/28.21.4157","article-title":"5-Methylcytosine DNA glycosylase activity is also present in the human MBD4 (G\/T mismatch glycosylase) and in a related avian sequence","volume":"28","author":"Zhu","year":"2000","journal-title":"Nucleic Acids Res."}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/96\/1\/72\/17673466\/kfl188.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,8,23]],"date-time":"2017-08-23T22:47:06Z","timestamp":1503528426000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article-lookup\/doi\/10.1093\/toxsci\/kfl188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,12,16]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2006,12,16]]},"published-print":{"date-parts":[[2007,3]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfl188","relation":{},"ISSN":["1096-0929","1096-6080"],"issn-type":[{"value":"1096-0929","type":"electronic"},{"value":"1096-6080","type":"print"}],"subject":[],"published":{"date-parts":[[2006,12,16]]}}}