NATURAL INHIBITOR OF COLONIC CELL DAMAGE

在本项目中，将进行研究，以评估 钙，食物的天然成分，对过度增殖和 结肠粘膜上皮细胞成熟受损， 对结肠癌易感性增加的个体。 测量 细胞增殖和分化将用作快速测定系统 评价口服钙剂在诱导 正常上皮细胞在结肠粘膜中的再增殖。 最近 啮齿类动物的研究结果表明，游离未酯化脂肪酸和 游离的未结合胆汁酸诱导结肠上皮细胞的损伤， 这种毒性可以通过相对适度地增加 结肠中的钙可用性。 我们现在已经在人类身上证明， 补充膳食钙可抑制 结肠上皮发生在结肠癌风险增加的个体中 癌 在这个项目中，基本的受控代谢研究将 在人类受试者身上进行，以确定钙的水平， 为此目的，饮食中所需的给药持续时间。 广泛 将进行测量，其中包括确定 胆汁酸和脂肪酸以游离形式和钙皂形式存在 钙的各种剂量方案，以及 结肠上皮细胞正常。 这些测量将进一步 扩展到研究所需的钙水平和 在一系列疾病中这些有益效果所需的管理 其特征在于对结肠癌的易感性增加。

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.