Brunaud Laurent, Alberto Jean-Marc, Ayav Ahmet, Gérard Philippe, Namour Farès, Antunes Laurent, Braun Marc, Bronowicki Jean-Pierre, Bresler Laurent, Guéant Jean-Louis
Laboratory of Cell and Molecular Pathology in Nutrition, INSERM EMI 0014 Medical Faculty, University of Nancy I, Vandoeuvre lès Nancy, France.
Clin Chem Lab Med. 2003 Aug;41(8):1012-9. doi: 10.1515/CCLM.2003.155.
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.
甲基的主要膳食来源（蛋氨酸和胆碱）缺乏会导致啮齿动物患肝癌。研究最为广泛的假说是，膳食甲基不足会导致DNA甲基化异常。维生素B12和叶酸在DNA甲基化中也起着重要作用，因为这两种辅酶是合成蛋氨酸和S-腺苷甲硫氨酸所必需的，而S-腺苷甲硫氨酸是维持DNA甲基化模式所需的常见甲基供体。本研究的目的是综述甲基缺乏饮食对大鼠DNA甲基化和肝癌发生的影响，并评估维生素B12状态在确定甲基缺乏饮食致癌性方面的作用。多项研究表明，甲基缺乏饮食会影响整体DNA甲基化。体内研究的证据尚未明确证实维生素B12与DNA甲基化之间的联系。我们报告称，维生素B12和低甲硫氨酸合成酶活性是DNA低甲基化的两个决定因素。胆碱或胆碱/蛋氨酸缺乏的饮食已被证明在12 - 24个月后会导致20 - 50%的动物患肝细胞癌。相比之下，除了胆碱、蛋氨酸和叶酸外，缺乏维生素B12会导致不到5%的大鼠患肝细胞癌。
