Molecular alterations in hepatocarcinogenesis induced by dietary methyl deficiency

A chronic deficiency of major dietary methyl group donors – methionine, choline, folic acid, and vitamin B12 – 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.