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A Comparison of the Effects of the Hypocholesteremic Agents, Cholestyramine and Candicidin, on the Induction of Intestinal Tumors in Rats by Azoxymethane¹

Department of Surgery, Wayne State University School of Medicine, Detroit, Michigan 48104

The effects of the ingestion of cholestyramine (2% in Purina rat chow) and candicidin (0.04%) on intestinal carcinogenesis by azoxymethane was studied in male Sprague-Dawley rats. Groups of 20 animals were given 8 mg of azoxymethane per kg per week for 25 weeks when the study was terminated. Although each drug affects lipid metabolism differently, they increased the number of intestinal tumors over those of controls to the same degree, from an average of 5 to 7.5 tumors per rat. There were no tumors in animals not injected with azoxymethane. The cholestyramine-treated group of rats developed significantly more tumors in the large intestine than did the other groups, whereas candicidin-fed rats had the greatest number of tumors in the distal small intestine. The feces of the cholestyramine-fed animals contained more total bile acids and a greater percentage of secondary bile acids than in normal animals. In the candicidin-treated group, the feces had increased amounts of cholesterol and its metabolites and also a greater degree of cholesterol degradation. These results suggest that bile acids have a greater promoting effect on tumorigenesis in the large intestine, whereas the effect of cholesterol and/or its degradation products is greater in the distal small intestine. These findings support the concept that the carcinogenic process may vary in the different segments of the intestinal tract.

¹ Supported by the Matilda R. Wilson Fund.

² To whom requests for reprints should be addressed.

³ Present address: Food and Drug Administration, 200 C Street S.W., Washington, D. C. 20204.

Received 2/ 9/77. Accepted 6/ 9/77.