The cotton-top tamarin (Saguinus oedipus) (Sgo) shows a high incidence of spontaneous colitis and subsequent adenocarcinoma of the colon after 5 years of life. As such, it is the only animal model which may suffer from a disease process closely analogous to that in humans. In man, colo-rectal cancer is believed to be caused by unknown carcinogens, co-carcinogens, and promoting agents. Epidemiologic studies have shown that diets high in fat, cholesterol, and/or meat and low in dietary fiber increase susceptibility to colitis and colon cancer. North Americans consuming high fat diets have increased levels of fecal bile acids and neutral sterols which have been implicated as promoting factors in human colon cancer. Experimental studies in in vivo and in vitro systems suggest that cholesterol may have a co-carcinogenic effect. This study is designed to determine whether the metabolism and excretion of cholesterol and bile acids in a monkey susceptible to colitis and colon cancer (Sgo) predispose it to colon cancer as compared to non-susceptible species. This study will also determine whether changes in the amount or type of dietary fat can significantly influence the pattern or magnitude of these metabolic characteristics and alter the eventual natural history of the colon cancer. In a 5 year study, two cohorts (20 animals each) of Sgo will be fed semipurified diets containing either a high or low fat content (42 vs 20% of calories as fat). Animals will be prospectively screened every four months for fecal neutral sterol and bile acid production, fecal enzyme activity (7-a-dehydroxylase, cholesterol dehydrogenase, and d-4-dehydrogenase), and fecal mutagenic load followed by endoscopy and biopsy of the colon. It is expected that the pattern of bile acids and neutral sterols in these animals, as well as mutagen and enzyme levels, will be predictors of eventual outcome as far as the development of colitis and/or colon cancer. In a second study, 12 Sgo, 12 Saguinus fuscicollis (Sgf), and 8 Saimiri sciureus will be fed diets varying the amount and type fo fat for 6 month periods. Stool collections taken near the end of each feeding trial will allow the measurement of the above biochemical parameters. Cholesterol absorption and total cholesterol turnover rates will be estimated using a double isotope method. Results from these studies will determine whether the concentrations and/or patterns of the measured parameters are affected by animal species and by dietary fat.
