Molecular alterations in hepatocarcinogenesis induced by dietary methyl deficiency

Abstract

A chronic deficiency of major dietary methyl group donors - methionine, choline, folic acid, and vitamin B 12 - can induce the development of liver cancer in rodents. Feeding methyl-deficient diets causes several molecular alterations, including altered lipid metabolism, oxidative stress, deregulated one-carbon metabolism, and a number of epigenetic abnormalities that result in progressive liver injury culminating in the development of primary liver tumors. Importantly, this methyl-deficient model of endogenous hepatocarcinogenesis is one of the most relevant models of human liver carcinogenesis that allows studying liver cancer pathogenesis by substantially complementing many shortcomings of humans-only studies. In this review, we describe molecular changes and their role in pathogenesis of liver carcinogenesis induced by methyl deficiency. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.