title: 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 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.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA. igor.pogribny@fda.hhs.gov
authors.forename: Igor P
authors.initials: IP
authors.lastname: Pogribny
authors.forename: S Jill
authors.initials: SJ
authors.lastname: James
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Beland
mesh_terms: D000818:Animals; D004249:DNA Damage; D019175:DNA Methylation; D003677:Deficiency Diseases / Q000150:complications* / Q000378:metabolism*; D004032:Diet; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008113:Liver Neoplasms / Q000209:etiology*; D008715:Methionine / Q000172:deficiency / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D018384:Oxidative Stress
chemical_list: D006657:Histones; D035683:MicroRNAs; D008715:Methionine