It has been shown that nutrient deficiencies, excesses and imbalances play an important role in the etiology of colon cancer. However, the modulating effects of most nutrients were studied individually with little regard for interacting effects with other nutrients. It is the primary objective of this proposal to gain new insights on the interaction of selenium, vitamin E, saturated fat (SFA) and polyunsaturated fat (PUFA) in colon carcinogenesis. Specifically, it is proposed to assess the role of dietary excess, adequacy or deficiency of selenium and vitamin E, individually and in combination, on azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats fed the diets containing high and low levels of PUFA and SFA. The effect of these diets on the activities of glutathione peroxidase and glutathione S-transferase in liver and colonic mucosa, on the levels of vitamin E and selenium in plasma and liver, on the composition of microsomal membrane fatty acids in liver and colonic mucosa, on testes weights and on fecal bile acid excretion will be determined in vehicle- and carcinogen-treated animals. From the carcinogenesis study and biochemical study, it is possible to identify a mechanism by which these interactive factors (selenium, vitamin E, SFA and PUFA) affect the carcinogenic process. At 35 days of age, groups of animals will be fed experimental diets containing various combinations of selenium, vitamin E, SFA and PUFA. At 50 days of age, all animals except vehicle controls will be given s.c. dose of AOM (29.6 mg/kg body wt., single dose). Some of the animals fed various diets will be used for the determination of the above-mentioned biochemical parameters. The remainder of the animals which die or are sacrificed as scheduled (30-32 weeks post-AOM injection) will be necropsied and colon tumor incidences compared between the various groups.
