{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T23:08:35Z","timestamp":1776121715397,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T00:00:00Z","timestamp":1499904000000},"content-version":"vor","delay-in-days":193,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>The carcinogenic potential of phenobarbital (PB) was assessed in a mouse line carrying a mutant <jats:italic>Mmh<\/jats:italic> allele of the <jats:italic>Mmh\/Ogg1<\/jats:italic> gene encoding the enzyme oxoguanine DNA glycosylase (Ogg1) responsible for the repair of 8\u2010hydroxy\u20102\u2032\u2010deoxyguanosine (8\u2010OHdG). <jats:italic>Mmh<\/jats:italic> homozygous mutant (<jats:italic>Ogg1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) and wild\u2010type (<jats:italic>Ogg1<\/jats:italic><jats:sup>+\/+<\/jats:sup>) male and female, 10\u2010week\u2010old, mice were treated with 500 ppm PB in diet for 78 weeks. Hepatocellular carcinomas (HCCs) were found in PB\u2010treated <jats:italic>Ogg1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, while <jats:italic>Ogg1<\/jats:italic><jats:sup>+\/+<\/jats:sup> animals developed only hepatocellular adenomas (HCAs) at the same rate. This was coordinated with PB\u2010induced significant elevation of 8\u2010OHdG formation in DNA and cell proliferation in adjacent liver of <jats:italic>Ogg1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Proteome analysis predicted activation of transcriptional factor Nrf2 in the livers and HCAs of PB\u2010administered <jats:italic>Ogg1<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice; however, its activation was insufficient or absent in the livers and HCCs of <jats:italic>Ogg1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, respectively. Significant elevation of phase I and II metabolizing enzymes was demonstrated in both <jats:italic>Ogg1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Ogg1<\/jats:italic><jats:sup>+\/+<\/jats:sup> animals. Treatment of <jats:italic>Ogg1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice with PB resulted in significant elevation of cell proliferation in the liver. These results indicate that PB induced progression from HCA to HCC in <jats:italic>Ogg1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, due to persistent accumulation of DNA oxidative base modifications and suppression of Nrf2\u2010mediated oxidative stress response, resulting in significant elevation of cell proliferation.<\/jats:p>","DOI":"10.1155\/2017\/8541064","type":"journal-article","created":{"date-parts":[[2017,7,13]],"date-time":"2017-07-13T21:02:43Z","timestamp":1499979763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Progression of Hepatic Adenoma to Carcinoma in <i>Ogg1<\/i> Mutant Mice Induced by Phenobarbital"],"prefix":"10.1155","volume":"2017","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1149-1450","authenticated-orcid":false,"given":"Anna","family":"Kakehashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Okuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Fujioka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1642-8127","authenticated-orcid":false,"given":"Min","family":"Gi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoji","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Wanibuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,13]]},"reference":[{"key":"e_1_2_8_1_2","first-page":"72","article-title":"The use of mutagenic and transgenic mice for the study of aging mechanisms and age pathology","volume":"7","author":"Anisimov V. 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