title: Moderate folate deficiency does not cause global hypomethylation of hepatic and colonic DNA or c-myc-specific hypomethylation of colonic DNA in rats.
abstract: Global and gene-specific DNA hypomethylation is considered to be an important early epigenetic event in several human neoplasms. A growing body of evidence has suggested that DNA methylation can be altered by dietary manipulation of methyl group donors. This study investigated whether moderate depletion of folate, a dietary component needed for the synthesis of methyl groups, would cause decreased hepatic and colonic S-adenosylmethionine concentrations, and thereby lead to global and/or protooncogene-specific DNA hypomethylation. Weanling rats were fed an amino acid-defined diet containing either 0 or 8 mg folate/kg diet for 15 or 24 wk. Significantly lower systemic, hepatic and colonic folate concentrations were observed in the moderately folate-depleted rats than in controls at both 15 and 24 wk (P < 0.005). Although hepatic S-adenosylmethionine was significantly lower in the moderately folate-depleted rats than in controls at the two time points (P < 0.03), colonic S-adenosylmethionine concentrations were not significantly different between the two groups at either time point. No significant differences between the folate-depleted and control animals could be detected with regard to global DNA methylation in the liver or colonic mucosa. Furthermore, c-myc protooncogene-specific DNA methylation in the colonic mucosa was not significantly different between these two groups of animals. These results indicate that moderate folate depletion does not cause a significant reduction in global DNA methylation in liver or colonic mucosa or in c-myc-specific colonic mucosal DNA methylation in this rat model.
authors.affiliation: Vitamin Bioavailability Laboratory, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
authors.forename: Y I
authors.initials: YI
authors.lastname: Kim
authors.forename: J K
authors.initials: JK
authors.lastname: Christman
authors.forename: J C
authors.initials: JC
authors.lastname: Fleet
authors.forename: M L
authors.initials: ML
authors.lastname: Cravo
authors.forename: R N
authors.initials: RN
authors.lastname: Salomon
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Ordovas
authors.forename: J
authors.initials: J
authors.lastname: Selhub
authors.forename: J B
authors.initials: JB
authors.lastname: Mason
mesh_terms: D000818:Animals; D001835:Body Weight; D003106:Colon / Q000737:chemistry* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D005492:Folic Acid / Q000494:pharmacology; D005494:Folic Acid Deficiency / Q000378:metabolism* / Q000503:physiopathology; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics*; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000378:metabolism; D008745:Methylation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000032:analysis / Q000378:metabolism
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D012436:S-Adenosylmethionine; D004247:DNA; D005492:Folic Acid; D008715:Methionine