NUTRITIONAL STRESS DIETS AND BIOMARKERS OF NEOPLASIA

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We have demonstrated in two studies that nutritional stress diets similar to the human Western-style diet (in terms of high fat, high phosphate, and low calcium and Vitamin content), given without any carcinogen, induced hyperproliferation and hyperplasia colonic crypts of mice and rats in 12 weeks. In a third study in mice, a nutritional stress diet continued for 20 weeks induced pathologic changes in colonic mucosa similar to early changes in rodent colon occurring in chemically-induced colonic carcinogenesis, and similar to pathological changes in human colon in individuals with colonic cancer. Increased dietary calcium intake inhibited these findings. In this project we will extend these studies to measure: (a) the effects of varying levels of calcium and Vitamin D in a nutritional stress diet that utilizes the fat components of a typical human (American Blend) diet; (b) determine the effects of nutritional stress diets on chemically induced (AOM) carcinogenesis of the colon; (c) in longer term studies of nutritional stress diets, without a carcinogen, measure the development of any advanced pathologic changes in the colon including dysplasia and adenoma formation, and the long-term consequences of nutritional stress diets, possibly to carcinogenesis. Thus, the proposed studies will determine the effects of different levels of calcium and Vitamin D on: the development of precancerous changes in the colon; the development of colonic neoplasia induced by nutritional stress diets without a carcinogen as well as with a carcinogen; and whether moderate alterations in calcium and Vitamin D intake can function as inhibitors of preneoplastic changes and neoplasia induced by the nutritional stress diets. In addition, these effects of the nutritional stress diets, and calcium and Vitamin D will be studied in other organs: mammary tissue, bladder and pancreas.