{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:17:30Z","timestamp":1789885050023,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,2,17]],"date-time":"2015-02-17T00:00:00Z","timestamp":1424131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005769","name":"National Institute for Environmental Studies","doi-asserted-by":"crossref","award":["0710AG333"],"award-info":[{"award-number":["0710AG333"]}],"id":[{"id":"10.13039\/501100005769","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005769","name":"National Institute for Environmental Studies","doi-asserted-by":"crossref","award":["1115AA082"],"award-info":[{"award-number":["1115AA082"]}],"id":[{"id":"10.13039\/501100005769","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research","award":["23390166"],"award-info":[{"award-number":["23390166"]}]},{"name":"Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research","award":["24790600"],"award-info":[{"award-number":["24790600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Methyl\u2010deficient diets are known to induce various liver disorders, in which DNA methylation changes are implicated. Recent studies have clarified the existence of the active DNA demethylation pathways that start with oxidization of 5\u2010methylcytosine (5meC) to 5\u2010hydroxymethylcytosine by ten\u2010eleven translocation (Tet) enzymes, followed by the action of base\u2013excision\u2013repair pathways. Here, we investigated the effects of a methionine\u2013choline\u2010deficient (MCD) diet on the hepatic DNA methylation of mice by precisely quantifying 5meC using a liquid chromatography\u2013electrospray ionization\u2013mass spectrometry and by investigating the regulatory pathways, including DNA demethylation. Although feeding the MCD diet for 1 week induced hepatic steatosis and lower level of the methyl donor\n                    <jats:italic>S<\/jats:italic>\n                    \u2010adenosylmethionine, it did not cause a significant reduction in the 5meC content. On the other hand, the MCD diet significantly upregulated the gene expression of the Tet enzymes, Tet2 and Tet3, and the base\u2013excision\u2013repair enzymes, thymine DNA glycosylase and apurinic\/apyrimidinic\u2010endonuclease 1. At the same time, the gene expression of DNA methyltransferase 1 and a, was also significantly increased by the MCD diet. These results suggest that the DNA methylation level is precisely regulated even when dietary methyl donors are restricted. Methyl\u2010deficient diets are well known to induce oxidative stress and the oxidative\u2010stress\u2010induced DNA damage, 8\u2010hydroxy\u20102\u2032\u2010deoxyguanosine (8OHdG), is reported to inhibit DNA methylation. In this study, we also clarified that the increase in 8OHdG number per DNA by the MCD diet is approximately 10 000 times smaller than the reduction in 5meC number, suggesting the contribution of 8OHdG formation to DNA methylation would not be significant. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/jat.3117","type":"journal-article","created":{"date-parts":[[2015,2,17]],"date-time":"2015-02-17T19:48:55Z","timestamp":1424202535000},"page":"1550-1556","source":"Crossref","is-referenced-by-count":32,"title":["The effect of a methyl\u2010deficient diet on the global DNA methylation and the DNA methylation regulatory pathways"],"prefix":"10.1002","volume":"35","author":[{"given":"Shota","family":"Takumi","sequence":"first","affiliation":[{"name":"Center for Environmental Health Sciences National Institute for Environmental Studies  Tsukuba 305\u20108506 Japan"},{"name":"Department of Public Health and Environmental Medicine The Jikei University School of Medicine  Tokyo 105\u20108461 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Okamura","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Sciences National Institute for Environmental Studies  Tsukuba 305\u20108506 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"Department of Public Health and Environmental Medicine The Jikei University School of Medicine  Tokyo 105\u20108461 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoharu","family":"Sano","sequence":"additional","affiliation":[{"name":"Center for Environmental Measurement and Analysis National Institute for Environmental Studies  Tsukuba 305\u20108506 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayoi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Sciences National Institute for Environmental Studies  Tsukuba 305\u20108506 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Nohara","sequence":"additional","affiliation":[{"name":"Center for Environmental Health Sciences National Institute for Environmental Studies  Tsukuba 305\u20108506 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