Effect of bile acids and dietary fat on large bowel carcinogenesis in animal models.

Epidemiologic and laboratory studies suggest that dietary fk actors, particularly high intake of fat and animal protein, and high concentration of bile acids and neutral sterols of the large bowel lumen are strongly associated with large bowel carcinogenesis. Such concepts guided our studies on animal models. Rats fed diets high in fat and/or protein had a higher incidence of DMH-induced large bowel tumors than rats fed standard diets. The source of fat and protein, animal vs. vegetable, had no major influence. High fat intake was associated with an increased excretion of fecal bile acids, particularly secondary bile acids, and neutral sterols. The repeated intrarectal doses of lithocholic acid or deoxycholic acid enhanced the development of MNNG-induced large bowel tumors in rats. Colostomized rats treated with intrarectal dose of MNNG had no tumors in the excluded segment. It suggests that luminal contents play a significant role in the induction of large bowel cancer. The results show that higher levels of bile acids in the large bowel lumen, resulting from high fat intake, exert a promoting effect on the development of large bowel cancer.