title: Effects of timing and quantity of chronic dietary ethanol consumption on azoxymethane-induced colonic carcinogenesis and azoxymethane metabolism in Fischer 344 rats.
abstract: Epidemiological studies have shown an association between consumption of alcoholic beverages and carcinoma of the large bowel, but studies in experimental models of colonic carcinogenesis have yielded conflicting results. We assessed the effects on azoxymethane-induced colonic carcinogenesis of both timing of chronic dietary ethanol consumption relative to carcinogen administration and quantity of ethanol consumption. Ten-week-old male Fischer 344 rats were given 11%, 22%, or 33% of calories as reagent ethanol or no ethanol by pair feeding with Lieber-DeCarli-type liquid diets providing comparable total carbohydrates, proteins, fats, and calories. Ten weekly s.c. injections of the bowel carcinogen azoxymethane (AOM), 7 mg/kg, were given to all rats in weeks 1-10. Three experimental groups were given their respective ethanol diet during acclimatization and AOM administration (preinduction and induction phases) and then were given the no-ethanol diet from week 11 until sacrifice in week 26 (postinduction phase). Three other groups received the no-ethanol diet during acclimatization and AOM administration and then were changed to their respective ethanol diet until sacrifice. The control AOM group received the no-ethanol diet throughout the study. Suppression of colonic tumorigenesis occurred in the groups with high levels of chronic dietary ethanol consumption during acclimatization and AOM administration: in the 33% and 22% diet groups, the prevalence of colonic tumors was 3% and 20% as compared with 50% in control (P less than 0.001 and P less than 0.02, respectively). Tumorigenesis in the left colon was more affected than in the right colon, as tumor prevalence in the left colon was decreased in both the 33% and 22% diet groups (0% in both versus 24% in control, P less than 0.005), whereas prevalence in the right colon was decreased only in the 33% diet group (3% versus 38%, P less than 0.001). By contrast, prevalence of colonic tumors in the 11% diet group was not significantly different from control. Chronic dietary ethanol consumption after AOM administration had no effect on tumor outcome, regardless of quantity of consumption. In an analogous study of [14C]AOM metabolism in rats fed the 33% diet during acclimatization and AOM administration, 14CO2 was exhaled at a slower rate than in rats fed no-ethanol diet (P = 0.05), indicating suppression of AOM metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000378:metabolism*; D001397:Azoxymethane / Q000378:metabolism* / Q000633:toxicity; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D003110:Colonic Neoplasms / Q000139:chemically induced*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D001391:Azo Compounds; D002250:Carbon Radioisotopes; D002245:Carbon Dioxide; D000431:Ethanol; D004247:DNA; D001397:Azoxymethane