Chronic alcohol consumption leads to substantial DNA hypomethylation as a result of significant reduction in tissue SAM. Rats fed alcohol for nine weeks showed a decrease in hepatic concentrations of SAM, methionine, and GSH as well as about 40-percent reduction in methylation (Lu et al. 2000). In addition, the investigators observed increased expression of a gene called c-myc and increased accumulation of breaks in the DNA strand, both of which predispose to hepatocellular carcinoma (HCC). In fact, chronic hepatic SAM deficiency in a certain mouse strain (i.e., Mat1a knockout mice) resulted in spontaneous development of HCC (Martinez-Chantar et al. 2002). Additionally, alcohol perturbs the folate cycle that is involved in methionine production and the generation of DNA building blocks (i.e., purines and pyrimidines) and which is integral to supplying the methyl groups necessary for DNA methylation.
