Methyl donors in the diet and responses to chemical carcinogens.

Dietary deficiency of labile methyl donors (choline and methionine) increases spontaneous and chemically induced hepatocarcinogenesis in rats. Chemical carcinogenesis in the colon, mammary gland, esophagus, and pancreas also may be increased. The mechanism of the dietary effect is not known but may be related to reduced methylation of DNA and RNA, hyperplasia of target cells, increased peroxidative damage, and altered carcinogen or promoter metabolism. Folate deficiency also is associated with increased carcinogenesis, an effect that may be mediated through participation in methyl metabolism; this has been less extensively studied. Deficiency of these three nutrients also may play a role in the elevated cancer risk in humans that is associated with ethanol intake.