Recent Studies on the Neoplasia and Abnormal Cellular Differentiation in Methyl Insufficiency

The induction of liver cancer by the dietary deficiencies of the methyl donors, methionine and choline, has been amply demonstrated in rodents. In light of the carcinogenic and cocarcinogenic activities of dietary methyl deprivation towards the liver, one would expect that deficiencies of vitamin B₁₂ and folate, responsible for the de novo biosynthesis of methyl groups, would similarly enhance the activities of carcinogens in vivo. Localized folate deficiency occurs in the oral mucosal cells of cigarette smokers. In addition, dietary deficiencies of vitamin B₁₂ and of folic acid have been shown to decrease the bioavailability of S-adenosylmethionine (SAM) in vivo. Clinical evidence for a causal link between B₁₂ deficiency and a hypomethylating environment in vivo came from an unexpected quarter: studies on the neuropathy seen in HIV-infected patients. The neuropathy seen in AIDS patients resembles that seen in experimental animals treated with nitrous oxide.