The effects of chronic ethanol consumption on carcinogen metabolism and on O6-methylguanine transferase-mediated repair of alkylated DNA.

This article presents a review and update of recent experiments conducted in collaboration with Dr. C. S. Lieber on mechanisms underlying the increased cancer risk associated with alcohol abuse. Ethanol has been found to be a potent inducer of microsomal enzymes involved in carcinogen metabolism in a variety of rat tissues including liver, esophagus, lungs, and intestines. In some of these tissues, ethanol's inductive effect on microsomal cytochrome P‐450 enzyme activity may result in enhanced levels of electrophilic metabolites of procarcinogens which are not readily detoxified. In addition, chronic ethanol feeding has been found to depress the activity of O6‐methylguanine transferase, an enzyme involved in the repair of carcinogen‐induced DNA alkylation. The effects of ethanol on carcinogen metabolism and on DNA repair would be expected to enhance the initiation phase of chemically induced cancers. Copyright © 1986, Wiley Blackwell. All rights reserved