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These functions of folate also depend on the availability of other B\u2010vitamins that participate in \u201cone\u2010carbon metabolism,\u201d including B2, B6 and B12. Our study therefore investigated whether combined dietary restriction of these vitamins amplifies aberrations in the epigenetic and genetic integrity of the <jats:italic>p53<\/jats:italic> gene that is induced by folate depletion alone. Ninety\u2010six mice were group pair\u2010fed diets with different combinations of B\u2010vitamin depletion over 10 weeks. DNA and RNA were extracted from epithelial cells isolated from the colon. Within the hypermutable region of <jats:italic>p53<\/jats:italic> (exons 5\u20138), DNA strand breaks were induced within exons 6 and 8 by folate combined with B2, B6 and B12 restriction (<jats:italic>p<\/jats:italic> &lt; 0.05); such effects were not significantly induced by mild folate depletion alone. Similarly, a minor degree of hypomethylation of exon 6 produced by isolated folate depletion was significantly amplified (<jats:italic>p<\/jats:italic> \u2264 0.05) by simultaneous depletion of all 4 B\u2010vitamins. Furthermore, the expression of <jats:italic>p53<\/jats:italic> and <jats:italic>MDM2<\/jats:italic> were significantly decreased (<jats:italic>p<\/jats:italic> \u2264 0.05) by the combined depletion state but not by folate depletion alone. These data indicate that inadequacies of other 1\u2010carbon vitamins may amplify aberrations of the <jats:italic>p53<\/jats:italic> gene induced by folate depletion alone, implying that concurrent inadequacies in several of these vitamins may have added tumorigenic potential beyond that observed with isolated folate depletion. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23599","type":"journal-article","created":{"date-parts":[[2008,5,22]],"date-time":"2008-05-22T19:46:49Z","timestamp":1211485609000},"page":"519-525","source":"Crossref","is-referenced-by-count":19,"title":["Multiple B\u2010vitamin inadequacy amplifies alterations induced by folate depletion in <i>p53<\/i> expression and its downstream effector <i>MDM2<\/i>"],"prefix":"10.1002","volume":"123","author":[{"given":"Zhenhua","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang\u2010Woon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy W.","family":"Crott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald E.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel B.","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,5,28]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2004.tb00070.x"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.suppl_1.1487"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1748"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/85798"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.22.010402.102932"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi100"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.2.283"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.4.750"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/153537020422901002"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.054718"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/85.11.875"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-129-7-199810010-00002"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.8.2350S"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-04-0419"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji116"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1207\/S15327914NC432_5"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.8.2204"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgg150"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1905840"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/65.1.46"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.8518"},{"key":"e_1_2_5_23_2","first-page":"1129","article-title":"Exon\u2010specific DNA hypomethylation of the p53 gene of rat colon induced by dimethylhydrazine. 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