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Vitamin B-12 deficiency creates aberrant DNA changes associated with cancer


Vitamin B-12 deficiency creates aberrant DNA changes associated with cancer
11 Jun 2004

"Derangements of one-carbon metabolism can directly affect the integrity of the genome by producing inappropriate uracil insertion into DNA and by altering patterns of DNA methylation. Vitamin B-12, a one-carbon nutrient, serves as a cofactor in the synthesis of precursors of biological methylation and in nucleotide synthesis. We therefore examined whether vitamin B-12 deficiency can induce these molecular anomalies in the colonic mucosa of rats," scientists in the United States report.

"Weanling male Sprague-Dawley rats (n0) were divided into 2 groups and fed either a vitamin B-12-deficient diet or a similar diet containing adequate amounts of the vitamin. Rats from each group were killed at 6 and 10 weeks (wk). Uracil misincorporation into DNA was measured by GC/MS and genomic DNA methylation was measured by LC/MS. Plasma vitamin B-12 concentrations in deficient rats were below detectable limits at 6 and 10 wk; in control rats, concentrations were 0.46±0.07 and 0.42±0.10 nmol/L at those times," wrote S.W. Choi and colleagues, Tufts University, Jean Mayer U.S. Department of Agriculture.

"Although the colon total folate concentration did not differ between the groups, the proportion that was methylfolate was marginally greater in the deficient rats at 10 wk (p=0.05) compared with control, consistent with the "methylfolate trap" that develops during vitamin B-12 deficiency. After 10 wk, the colonic DNA of the deficient rats displayed a 35% decrease in genomic methylation and a 105% increase in uracil incorporation (p<0.05)."

"This vitamin B-12-deficient diet, which was of insufficient severity to cause anemia or illness, created aberrations in both base substitution and methylation of colonic DNA, which might increase susceptibility to carcinogenesis," researchers concluded.

Choi and colleagues published their study in Journal of Nutrition (Vitamin B-12 deficiency induces anomalies of base substitution and methylation in the DNA of rat colonic epithelium. J Nutr, 2004;134(4):750-755).

For additional information, contact S.W. Choi, Tufts University, Jean Mayer U.S. Department Agriculture, Human Nutrition Research Center Aging, Vitamins & Carcinogenesis Laboratory, Boston, MA 02111 USA.

The publisher's contact information for the Journal of Nutrition is: American Institute of Nutrition, 9650 Rockville Pike, Bethesda, MD 20814 USA.

The information in this article comes under the major subject areas of Diet and Nutrition and Oncogenesis. This article was prepared by Biotech Week editors from staff and other reports. Copyright 2004, Biotech Week via &

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