{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:05:47Z","timestamp":1790233547182,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,4]]},"DOI":"10.1093\/toxsci\/kfp031","type":"journal-article","created":{"date-parts":[[2009,2,22]],"date-time":"2009-02-22T03:46:09Z","timestamp":1235274369000},"page":"273-289","source":"Crossref","is-referenced-by-count":32,"title":["Multiple Genes Exhibit Phenobarbital-Induced Constitutive Active\/Androstane Receptor\u2013Mediated DNA Methylation Changes during Liver Tumorigenesis and in Liver Tumors"],"prefix":"10.1093","volume":"108","author":[{"given":"Jennifer M.","family":"Phillips","sequence":"first","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":[[2009,2,20]]},"reference":[{"key":"key\n\t\t\t\t20170508175449_bib1","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1126\/science.1154884","article-title":"Generation of pluripotent stem cells from adult mouse liver and stomach cells","volume":"321","year":"2008","journal-title":"Science"},{"key":"key\n\t\t\t\t20170508175449_bib2","first-page":"7812","article-title":"Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of beta-catenin-mutated mouse liver tumors","volume":"22","year":"2001","journal-title":"Oncogene"},{"key":"key\n\t\t\t\t20170508175449_bib3","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/toxsci\/kfj091","article-title":"Diethanolamine and phenobarbital produce an altered pattern of methylation in GC-rich regions of DNA in B6C3F1 mouse hepatocytes similar to that resulting from choline deficiency","volume":"90","year":"2006","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170508175449_bib4","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","year":"2006","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170508175449_bib5","first-page":"3918","article-title":"Morphological classification of mouse liver tumors based on biological characteristics","volume":"42","year":"1982","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170508175449_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","year":"1991","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"key\n\t\t\t\t20170508175449_bib7","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/(SICI)1098-2744(199702)18:2<97::AID-MC5>3.0.CO;2-N","article-title":"Comparison of effect of tumor promoter treatments on DNA methylation status and gene expression in B6C3F1 and C57BL\/6 mouse liver and in B6C3F1 mouse liver tumors","volume":"18","year":"1997","journal-title":"Mol. Carcinog."},{"key":"key\n\t\t\t\t20170508175449_bib8","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","year":"1996","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20170508175449_bib9","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1056\/NEJMra072067","article-title":"Epigenetics in cancer","volume":"358","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"key\n\t\t\t\t20170508175449_bib10","first-page":"4014","article-title":"Mutational analysis of the H-ras oncogene in spontaneous C57BL\/6 x C3H\/He mouse liver tumors and tumors induced with genotoxic and nongenotoxic hepatocarcinogens","volume":"50","year":"1990","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170508175449_bib11","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1146\/annurev.biochem.74.010904.153721","article-title":"Eukaryotic cytosine methyltransferases","volume":"74","year":"2005","journal-title":"Annu. Rev. Biochem."},{"key":"key\n\t\t\t\t20170508175449_bib12","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1146\/annurev.pharmtox.42.092001.141143","article-title":"Altered DNA methylation: A secondary mechanism involved in carcinogenesis","volume":"42","year":"2002","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"key\n\t\t\t\t20170508175449_bib13","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","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"key\n\t\t\t\t20170508175449_bib14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1242\/dev.113.1.119","article-title":"Methylation levels of maternal and paternal genomes during preimplantation development","volume":"113","year":"1991","journal-title":"Development"},{"key":"key\n\t\t\t\t20170508175449_bib15","doi-asserted-by":"crossref","first-page":"4156","DOI":"10.1073\/pnas.0630614100","article-title":"Induction of bilirubin clearance by the constitutive androstane receptor (CAR)","volume":"100","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"key\n\t\t\t\t20170508175449_bib16","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\t20170508175449_bib17","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1126\/science.1164368","article-title":"Core signaling pathways in human pancreatic cancers revealed by global genomic analyses","volume":"321","year":"2008","journal-title":"Science"},{"key":"key\n\t\t\t\t20170508175449_bib18","doi-asserted-by":"crossref","first-page":"6318","DOI":"10.1128\/MCB.19.9.6318","article-title":"Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene","volume":"19","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"key\n\t\t\t\t20170508175449_bib19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1006\/faat.1996.0025","article-title":"Subchronic effects of dieldrin and phenobarbital on hepatic DNA synthesis in mice and rats","volume":"29","year":"1996","journal-title":"Fundam. Appl. Toxicol."},{"key":"key\n\t\t\t\t20170508175449_bib20","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1093\/carcin\/17.5.947","article-title":"Dose dependence of phenobarbital promotion of preneoplastic hepatic lesions in F344 rats and B6C3F1 mice: Effects on DNA synthesis and apoptosis","volume":"17","year":"1996","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20170508175449_bib21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.2133\/dmpk.23.8","article-title":"The roles of nuclear receptors CAR and PXR in hepatic energy metabolism","volume":"23","year":"2008","journal-title":"Drug Metab. Pharmacokinet."},{"key":"key\n\t\t\t\t20170508175449_bib22","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1038\/sj.bjc.6604374","article-title":"Proteins that bind methylated DNA and human cancer: Reading the wrong words","volume":"98","year":"2008","journal-title":"Br. J. Cancer"},{"key":"key\n\t\t\t\t20170508175449_bib42","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature07385","article-title":"Comprehensive genomic characterization defines human glioblastoma genes and core pathways","volume":"455","year":"2008","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170508175449_bib23","first-page":"5087","article-title":"Lack of phenobarbital-mediated promotion of hepatocarcinogenesis in connexin 32-null mice","volume":"15","year":"2000","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170508175449_bib24","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1126\/science.1140485","article-title":"Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production","volume":"317","year":"2007","journal-title":"Science"},{"key":"key\n\t\t\t\t20170508175449_bib25","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.cell.2008.06.009","article-title":"The colorful history of active DNA demethylation","volume":"133","year":"2008","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170508175449_bib26","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.cell.2005.02.034","article-title":"Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1\/CXCL12 secretion","volume":"121","year":"2005","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170508175449_bib27","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1126\/science.1164382","article-title":"An integrated genomic analysis of human glioblastoma multiforme","volume":"321","year":"2008","journal-title":"Science"},{"key":"key\n\t\t\t\t20170508175449_bib28","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/toxsci\/kfn063","article-title":"Identification of genes that may play critical roles in phenobarbital (PB)-induced liver tumorigenesis due to altered DNA methylation","volume":"104","year":"2008","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170508175449_bib29","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1093\/toxsci\/kfl188","article-title":"Orphan nuclear receptor constitutive active\/androstane receptor-mediated alterations in DNA methylation during phenobarbital promotion of liver tumorigenesis","volume":"96","year":"2007","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170508175449_bib30","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/nrc1235","article-title":"Comparative biology of mouse versus human cells: Modeling human cancer in mice","volume":"3","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"key\n\t\t\t\t20170508175449_bib31","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/mc.2940090307","article-title":"Alterations in the methylation status and expression of the raf oncogene in phenobarbital-induced and spontaneous B6C3F1 mouse live tumors","volume":"9","year":"1994","journal-title":"Mol. Carcinog."},{"key":"key\n\t\t\t\t20170508175449_bib32","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/35102167","article-title":"Stem cells, cancer, and cancer stem cells","volume":"414","year":"2001","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170508175449_bib33","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1093\/carcin\/12.12.2331","article-title":"Analysis of the Ha-ras oncogene in C3H\/He mouse liver tumours derived spontaneously or induced with diethylnitrosamine or phenobarbitone","volume":"12","year":"1991","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20170508175449_bib34","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","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"key\n\t\t\t\t20170508175449_bib35","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1096\/fasebj.9.14.7589980","article-title":"Liver regeneration","volume":"9","year":"1995","journal-title":"FASEB J."},{"key":"key\n\t\t\t\t20170508175449_bib36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1093\/toxsci\/kfl041","article-title":"PCB 153, a non-dioxin-like tumor promoter, selects for beta-catenin (Catnb)-mutated mouse liver tumors","volume":"93","year":"2006","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170508175449_bib37","doi-asserted-by":"crossref","first-page":"6043","DOI":"10.1074\/jbc.274.10.6043","article-title":"The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene","volume":"274","year":"1999","journal-title":"J. Biol. Chem."},{"key":"key\n\t\t\t\t20170508175449_bib38","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1124\/mol.107.042960","article-title":"PPP1R16A, the membrane subunit of protein phosphatase 1beta, signals nuclear translocation of the nuclear receptor constitutive active\/androstane receptor","volume":"73","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"key\n\t\t\t\t20170508175449_bib39","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1053\/jhep.2001.24172","article-title":"The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR","volume":"33","year":"2001","journal-title":"Hepatology"},{"key":"key\n\t\t\t\t20170508175449_bib40","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1210\/me.2003-0397","article-title":"CAR, driving into the future","volume":"18","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"key\n\t\t\t\t20170508175449_bib41","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","year":"2007","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170508175449_bib43","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","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"key\n\t\t\t\t20170508175449_bib44","article-title":"The impact of metabolism on DNA methylation","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"key\n\t\t\t\t20170508175449_bib45","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1080\/15287399109531574","article-title":"Hypomethylation of ras oncogenes in chemically induced and spontaneous B6C3F1 mouse liver tumors","volume":"34","year":"1991","journal-title":"Toxicol. Environ. Health"},{"key":"key\n\t\t\t\t20170508175449_bib46","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","year":"2002","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t20170508175449_bib47","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\t20170508175449_bib48","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nature05944","article-title":"In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state","volume":"448","year":"2007","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170508175449_bib49","first-page":"53","article-title":"Phenobarbital mechanistic data and risk assessment: Enzyme induction, enhanced cell proliferation, and tumor promotion","volume":"71","year":"1996","journal-title":"Pharmacol. Ther."},{"key":"key\n\t\t\t\t20170508175449_bib50","doi-asserted-by":"crossref","first-page":"5825","DOI":"10.1073\/pnas.83.16.5825","article-title":"Activating mutations of the c-Ha-ras protooncogene in chemically induced hepatomas of the male B6C3 F1 mouse","volume":"83","year":"1986","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"key\n\t\t\t\t20170508175449_bib51","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0003-9861(02)00456-3","article-title":"The role of the nuclear receptor CAR as a coordinate regulator of hepatic gene expression in defense against chemical toxicity","volume":"409","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"key\n\t\t\t\t20170508175449_bib52","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\t20170508175449_bib53","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nature07314","article-title":"In vivo reprogramming of adult pancreatic exocrine cells to \u03b2-cells","volume":"455","year":"2008","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170508175449_bib54","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/ar1963","article-title":"Relevance of the stroma and epithelial-mesenchymal transition (EMT) for the rheumatic diseases","volume":"8","year":"2006","journal-title":"Arthritis Res. Ther."}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/108\/2\/273\/16680302\/kfp031.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T04:40:56Z","timestamp":1633149656000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article-lookup\/doi\/10.1093\/toxsci\/kfp031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,20]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,2,20]]},"published-print":{"date-parts":[[2009,4]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfp031","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,20]]}}}