Alcohol-related Diseases and Carcinogenesis
AbstractPossible mechanisms whereby alcohol abuse and alcohol-related diseases may promote the development of cancer are analyzed. The mechanisms discussed include: ( a ) contact-related local effects on the upper gastrointestinal tract; ( b ) the presence of low levels of carcinogens in alcoholic beverages; ( c ) induction of microsomal enzymes involved in carcinogen metabolism; ( d ) various types of cellular injury produced by ethanol and its metabolites and their relationship to cancer, particularly in the liver; ( e ) the nutritional disturbances frequently associated with alcohol abuse. The relationship between alcohol-induced cirrhosis and hepatocellular carcinoma is also discussed, and case histories of patients seen at the Bronx Veterans Administration Medical Center with hepatocellular carcinoma in the absence of cirrhosis are reviewed. Data are presented demonstrating the induction, by chronic ethanol consumption, of microsomal enzymes which convert procarcinogens to carcinogens. These data were derived from experiments in which the ability of microsomes isolated from liver, intestine, and lung tissues of ethanol-fed and control rats to activate several test carcinogens was examined in the Ames Salmonella -mutagenicity test. The hypothesis is presented that ethanol-mediated induction of enzyme systems which activate procarcinogens to carcinogens in various tissues contributes to the enhanced incidence of cancer in the alcoholic. 1 Presented at the Alcohol and Cancer Workshop, October 23 and 24, 1978, Bethesda, Md. Original studies were supported in part by the Medical Research Service of the Veterans Administration and USPHS Grants AA03508, AA00224, AM12511, and CA22354; by American Cancer Society Grant BC 200A, and by the Deutsche Forschungsgemeinschaft (Se 333/2).