NATURAL INHIBITOR OF COLONIC CELL DAMAGE

在这个项目中，将进行研究，以评估 钙，食物的天然成分，对过度增殖和 大鼠结肠粘膜上皮细胞成熟障碍 结肠癌易感性增加的个体。测量 细胞增殖和分化将作为一种快速检测系统 口服补钙在诱导中的作用 结肠粘膜与正常上皮细胞的再繁殖。近期 在啮齿动物身上的研究结果表明，游离未酯化脂肪酸和 游离未结合胆汁酸引起结肠上皮细胞损伤 这种毒性可以通过相对温和的增加 结肠中钙的利用率。我们现在已经在人类身上证明了 补充膳食钙可抑制心肌细胞的过度增殖反应 结肠上皮出现在结肠癌风险增加的个体中 癌症。在这个项目中，基础受控代谢研究将是 在人体受试者身上进行，以测定钙和 为此目的，饮食中需要的给药持续时间。广泛性 将进行测量，其中将包括确定 胆汁酸和脂肪酸以游离形式和钙肥皂形式存在 不同的钙剂量计划，以及钙的再充盈程度 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持续时间 在一系列疾病中产生这些有益效果所需的管理 以结肠癌易感性增加为特征的。

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.