NATURAL INHIBITOR OF COLONIC CELL DAMAGE

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In this project studies will be carried out to assess the effect of calcium, an natural constituent of food, on the hyperproliferation and impaired maturation of colonic epithelial cells occurring in the mucosa of individuals with increased susceptibility to colon cancer. Measurements of cell proliferation and differentiation will serve as a rapid assay system to evaluate the utility of oral supplementary calcium in inducing repopulation of the colonic mucosa with normal epithelial cells. Recent findings in rodents have indicated that free unesterified fatty acids and free unconjugated bile acids induce damage of colonic epithelial cells, and that this toxicity can be neutralized by a relatively modest increase in calcium availability in the colon. We have now shown in humans that supplementary dietary calcium inhibits a hyperproliferative response of colonic epithelium occurring in individuals at increased risk for colon cancer. In this project, basic controlled metabolic studies will be carried out on the human subjects to determine levels of calcium and durations of administration needed in the diet for this purpose. Extensive measurements will be made which will include determination of the levels of bile acids and fatty acids present in free form and as calcium soaps under various dosage schedules of calcium, and the degree of repopulation of the colon with normal epithelial cells. These measurements will be further extended to study the levels of calcium required and durations of administration needed for these beneficial effects in a series of diseases characterized by increased susceptibility to colon cancer.