You are here: Home :: Area NEM :: Medical science :: Human medicine

Laurent Brunaud, Jean-Marc Alberto, Ahmet Ayav, Philippe Gérard, Farès Namour, Laurent Antunes, Marc Braun, Jean-Pierre Bronowicki, Laurent Bresler, Jean-Louis Guéant

Effects of Vitamin B12 and Folate Deficiencies on DNA Methylation and Carcinogenesis in Rat Liver

Deficiencies of the major dietary sources of methyl groups, methionine and choline, lead to the formation of liver cancer in rodents. The most widely investigated hypothesis has been that dietary methyl insufficiency results in abnormal DNA methylation. Vitamin B₁₂ and folate also play important roles in DNA methylation since these two coenzymes are required for the synthesis of methionine and S-adenosyl methionine, the common methyl donor required for the maintenance of methylation patterns in DNA. The aim of this study was to review the effects of methyl-deficient diets on DNA methylation and liver carcinogenesis in rats, and to evaluate the role of vitamin B₁₂ status in defining carcinogenicity of a methyl-deficient diet. Several studies have shown that a methyl-deficient diet influences global DNA methylation. Evidence from in vivo studies has not clearly established a link between vitamin B₁₂ and DNA methylation. We reported that vitamin B₁₂ and low methionine synthase activity were the two determinants of DNA hypomethylation. Choline- or choline/methionine-deficient diets have been shown to cause hepatocellular carcinoma in 20–50% of animals after 12–24 months. In contrast, the effect of vitamin B₁₂ withdrawal, in addition to choline, methionine and folate, induced hepatocellular carcinoma in less than 5% of

Clinical Chemical Laboratory Medicine, Walter de Gruyter

Print ISSN: 1434-6621
Volume: 41, 08/2003
Pages: 1012 - 1019

Show full article (external site)

Show all available items of this journal

 

Area NEM