Methyl Groups in Carcinogenesis: Effects on DNA Methylation and Gene Expression.

摘要: Abstract Lipotrope-deficient (methyl-deficient) diets cause fatty livers and increased liver-cell turnover promote carcinogenesis in rodents. In rats prolonged intake of methyl-deficient results liver tumor development. The mechanisms responsible for the cancer-promoting carcinogenic properties this deficiency remain unclear. experiments described here lend support to hypothesis that such a diet, by causing depletion S-adenosylmethionine pools, DNA hypomethylation, which turn leads changes expression genes may have key roles regulation growth. fed severely diet (MDD), lowered pools hypomethylated were observed within 1 week. extent hypomethylation when MDD was longer periods. decreases overall levels methylation accompanied simultaneous alterations gene expression, yielding patterns closely resembled those reported occur animals exposed chemicals hepatomas. Northern blot analysis polyadenylated RNAs from control or deficient showed that, after week intake, there large increases mRNAs c-myc c-fos oncogenes, somewhat smaller c-Ha-ras mRNA, virtually no change c-Ki-ras mRNA. contrast, epidermal growth factor receptor decreased significantly. elevated c-myc, c-fos, selective sequences specifying these genes. Changes induced month gradually reversed restoration an adequate diet. hepatomas dietary methyl deficiency, abnormal. Although human are unlikely be as used experiments, some parts world low methionine choline contaminated with mycotoxins, aflatoxin, common. Even industrialized nations, deficiencies folic acid vitamin B12 not uncommon exacerbated therapeutic agents substance abuse. Thus, it seems possible interactions contaminants drugs, inducing aberrant contribute cancer causation humans.