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Mol Nutr Food Res. 2012 Jan;56(1):116-25. doi: 10.1002/mnfr.201100524. Epub 2011 Nov 17.

Molecular alterations in hepatocarcinogenesis induced by dietary methyl deficiency.

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Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.


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.

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