ABSTRACT
A central role in chemical carcinogenesis of dietary methyl supply and of methyl metabolism is increasingly apparent. Methyl groups are supplied in the diet principally by methionine and choline, and normal methyl metabolism requires, in addition, the nutrients folate and vitamin B12. Deficiencies of choline, methionine or folate are of widely varying importance in humans, with folate deficiency being by far the most important. Folate deficiency can arise in pregnancy, alcoholism, malabsorption, exposure to several therapeutic drugs and, notably, exposure to the antifolate cancer chemotherapeutic drugs such as methotrexate (MTX). MTX-treated patients manifest markedly reduced plasma methionine, which indicates perturbation of methyl as well as folate metabolism by the drug. Mammary gland epithelium concentrates choline and folate from the blood and secretes milk containing large amounts of folate bound to folate-binding proteins and large amounts of choline. The gland can also synthesize choline.
