Enhancement of 1,2-dimethylhydrazine-induced rectal carcinogenesis following chronic ethanol consumption in the rat.
The incidence, distribution, size, and histopathology of grossly visible intestinal tumors induced by the parenteral administration of 1,2-dimethylhydrazine dihydrochloride were examined in 32 paired rats fed a nutritionally adequate liquid diet containing 36% of total calories either as ethanol or isocaloric carbohydrates. The liquid diets were begun 4 wk before the first of four weekly injections of 1,2-dimethylhydrazine dihydrochloride. At the time of the subcutaneous application of the procarcinogen, liquid diets were omitted for 3 wk, and were replaced by a standard laboratory diet. This feeding schedule was repeated four times, and after 32 wk the animals were killed. Chronic ethanol ingestion increased the total number of rectal tumors significantly (17 vs. 6, p less than 0.02). However, alcohol had no effect on tumor size or histopathology. Chronic ethanol ingestion did not exhibit any cocarcinogenic effect in tissues other than the rectum. A 47% increase in the activity of mucosal alcohol dehydrogenase in the distal colorectum was found between chronically ethanol-fed rats and pair-fed controls (0.241 +/- 0.019 vs. 0.164 +/- 0.020 mumol X mg protein-1 X h-1, p less than 0.01). This could in part explain the cocarcinogenic effect of alcohol in this tissue. Fecal bile acids, however, do not play a role as promoters of rectal cancer under the present experimental conditions. The data give experimental support to the epidemiologic findings of an increased incidence of rectal cancer in the alcoholic.
D000230:Adenocarcinoma / Q000139:chemically induced; D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis; D004032:Diet; D004127:Dimethylhydrazines; D000431:Ethanol / Q000009:adverse effects*; D005243:Feces / Q000032:analysis; D007417:Intestinal Polyps / Q000139:chemically induced; D008297:Male; D008763:Methylhydrazines; D051381:Rats; D011919:Rats, Inbred Strains; D012004:Rectal Neoplasms / Q000139:chemically induced* / Q000201:enzymology
D001647:Bile Acids and Salts; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D000431:Ethanol; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase