MODERATE FOLATE-DEFICIENCY DOES NOT CAUSE GLOBAL HYPOMETHYLATION OF HEPATIC AND COLONIC DNA OR C-MYC-SPECIFIC HYPOMETHYLATION OF COLONIC DNA IN RATS

Global and gene-specific DNA hypomethylation is considered to be an im portant early epigenetic event in several human neoplasms. A growing b ody of evidence has suggested that DNA methylation can be altered by d ietary manipulation of methyl group donors. This study investigated wh ether 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/o r protooncogene-specific DNA hypomethylation, Weanling rats were fed a n amino acid-defined diet containing either 0 or 8 mg folate/kg diet f or 15 or 24 wk. Significantly lower systemic, hepatic and colonic fola te 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-d epleted rats than in controls at the two time points (P < 0.03), colon ic S-adenosylmethionine concentrations were not significantly differen t between the two groups at either time point. No significant differen ces 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 colon ic mucosa was not significantly different between these two groups of animals. These results indicate that moderate folate depletion does no t 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.