title: Effects of vitamin B12 and folate deficiencies on DNA methylation and carcinogenesis in rat liver.
abstract: 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 rats.
authors.affiliation: Laboratory of Cell and Molecular Pathology in Nutrition, INSERM EMI 0014 Medical Faculty, University of Nancy I, Vandoeuvre lès Nancy, France. lbrunaud@planete.net
authors.forename: Laurent
authors.initials: L
authors.lastname: Brunaud
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Alberto
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ayav
authors.forename: Philippe
authors.initials: P
authors.lastname: Gérard
authors.forename: Farès
authors.initials: F
authors.lastname: Namour
authors.forename: Laurent
authors.initials: L
authors.lastname: Antunes
authors.forename: Marc
authors.initials: M
authors.lastname: Braun
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.forename: Laurent
authors.initials: L
authors.lastname: Bresler
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage; D002794:Choline / Q000008:administration & dosage; D002796:Choline Deficiency / Q000378:metabolism / Q000503:physiopathology; D019175:DNA Methylation; D004032:Diet; D005494:Folic Acid Deficiency / Q000378:metabolism / Q000503:physiopathology*; D005743:Gastrectomy; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008715:Methionine / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D014806:Vitamin B 12 Deficiency / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D002273:Carcinogens; D008715:Methionine; D002794:Choline