An epidemiologic association has been reported between consumption of alcoholic beverages, particularly beer, and large bowel carcinoma, the most common cancer in the United States. We propose to determine if there is experimental support for this epidemiologic association in the azoxymethane-treated-rat model of colon carcinoma and to obtain evidence regarding the possible mechanisms leading to the association. The hypothesis to be tested is that beer and ethanol consumption will increase large bowel carcinogenesis in the model by increasing fecal levels of bile acids and neutral sterols, known promoters of colon carcinogenesis. We will administer either beer, which contains congeners and contaminants as well as ethanol, or reagent grade ethanol which lacks these substances, in liquid diets at two dosage levels to male Fischer 344 rats. Carcinogen-treated rats will receive the intestinal carcinogen azoxymethane. Blood ethanol levels will be monitored. Fecal samples will be analyzed for bile acid and neutral sterol levels and for changes in bacterial flora. At necropsy the entire gastrointestinal tract will be studied for tumor formation. The relationships between tumor characteristics, fecal chemistry, and fecal microbiology will be analyzed, and the findings will be related to the hypothesis.
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| Sohn, O S; Fiala, E S; Puz, C et al. (1987) Enhancement of rat liver microsomal metabolism of azoxymethane to methylazoxymethanol by chronic ethanol administration: similarity to the microsomal metabolism of N-nitrosodimethylamine. Cancer Res 47:3123-9 |
