Epigenetics of Dietary Methyl-Group Donor Deficiency and Liver Cancer

  • Aline de ContiEmail author
  • Igor P. Pogribny
Reference work entry


Food, nutritional factors, and dietary habits play a fundamental role in the etiology of cancer and contribute greatly to the development of liver cancer. One of the best characterized nutritional models of liver carcinogenesis that resembles the development of liver cancer in humans is dietary methyl donor deficiency in rodents. This model has been extensively studied, and the results have identified clearly non-genotoxic epigenetic alterations, especially methylation of DNA and histone proteins, as the underlying mechanism of the liver cancer development. Importantly, this methyl-deficient model allows the identification of early epigenetic alterations that persist during liver cancer development and that may be used as diagnostic biomarkers. The correction of epigenetic alterations by dietary interventions is a promising avenue for cancer control and prevention strategies.


Betaine Choline Folic acid Hepatocarcinogenesis Histones methylation Liver cancer Methionine Methyl-deficient diet Methyl donors S-Adenosylmethionine One-carbon metabolism 

List of Abbreviations






Betaine-homocysteine S-methyltransferase


Cystathionine β-synthase


Cystathionine y-lyase


DNA methyltransferases


Glycine N-methyltransferase




Histone H3 lysine 9 (H3K9) and histone H4 lysine 20


Hepatitis B


Hepatocellular carcinoma


Hepatitis C




Methionine adenosyltransferase


Methionine adenosyltransferase 1 alpha


Methyl-group donor-deficient




Methionine synthase






Methylenetetrahydrofolate reductase


Nonalcoholic fatty liver disease




SAH hydrolase




Ten-eleven translocation methylcytosine dioxygenase enzymes






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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Biochemical ToxicologyNational Center for Toxicological Research, Food and Drug AdministrationJeffersonUSA

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