Role of bile metabolites in colon carcinogenesis. Animal models

Epidemiological data indicate that colon cancer incidence is associated mainly with high dietary fat intake. Studies in metabolic epidemiology have shown a strong association between dietary fat intake, level of fecal bacteria, fecal acid, and neutral sterols, and the risk of colon cancer among different populations. Current concepts visualize that colonic bile acids and cholesterol metabolities play a modifying role in large bowel carcinogenesis, and that these compounds are derived from dietary factors, directly or indirectly, and subsequently are modified by the intestinal bacteria. In animal models, lithocholic acid and dexycholic acid, which are present in high concentration in the large bowel of man, acted as promoters of colon carcinogenesis. The carcinogenic effect of azoxymethane in rats was enhanced by the increase of bile salts in the colon induced by surgical means. Animals fed a high fat diet were more susceptable to colon tumor induction by dimethylhydrazine compared with rats fed a normal diet. Our data also demonstrate that the intestinal microflora played a modifying role in accelerating colon tumor production by dimethylhydrazine.