NUTRITIONAL STRESS DIETS AND BIOMARKERS OF NEOPLASIA

我们在两项研究中证明，营养压力饮食类似于 人类西式饮食（高脂肪，高磷酸盐， 低钙和维生素含量），不含任何致癌物质， 12只小鼠和大鼠结肠隐窝过度增殖和增生 周 在第三项小鼠研究中，营养应激饮食持续了 20周诱导的结肠粘膜病理变化与早期相似 在化学诱导的结肠中发生的啮齿动物结肠的变化 致癌作用，并类似于人类结肠的病理变化， 结肠癌患者 增加膳食钙摄入量 抑制了这些发现。 在这个项目中，我们将把这些研究扩展到 措施： (a)不同水平的钙和维生素D的影响， 利用典型人类的脂肪成分的营养应激饮食 （American Blend）diet; (b)确定营养应激饮食对化学 诱导（AOM）结肠癌发生; (c)在营养压力饮食的长期研究中，如果没有 致癌物质，测量任何先进的病理变化的发展， 结肠包括异型增生和腺瘤形成， 营养压力饮食的后果，可能致癌。 因此，拟议的研究将确定不同水平的影响， 钙和维生素D的作用： 结肠;营养应激诱导的结肠肿瘤的发展 不含致癌物和含致癌物的饮食;以及 钙和维生素D摄入量的适度改变可以起到 肿瘤前变化和肿瘤形成的抑制剂 营养应激饮食 此外，营养的这些影响 压力饮食，钙和维生素D将在其他器官中进行研究： 乳腺组织膀胱和胰腺

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.