• DNA methylation;
  • Hepatocarcinogenesis;
  • Histone methylation;
  • Methyl-deficient diet;
  • MicroRNA


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.