MACRO AND MICRONUTRIENT INTERACTION IN COLON CANCER

它已被证明，营养不足，过量和不平衡发挥作用， 在结肠癌病因学中的重要作用。 然而，调制 大多数营养素的影响是单独研究的， 与其他营养素的相互作用。 这是首要目标， 这一提议旨在获得关于硒、维生素 E、结肠中的饱和脂肪（SFA）和多不饱和脂肪（PUFA） 致癌作用 具体而言，建议评估饮食的作用， 硒和维生素E的过量、充足或缺乏， 联合使用对氧化偶氮甲烷（AOM）诱导的男性结肠癌发生的影响 F344大鼠饲喂含有高和低水平PUFA和SFA的饮食。 这些饲料对谷胱甘肽过氧化物酶和谷胱甘肽过氧化物酶活性的影响 谷胱甘肽S-转移酶在肝脏和结肠粘膜，对水平 维生素E和硒在血浆和肝脏中的组成， 肝脏和结肠粘膜微粒体膜脂肪酸，睾丸 将在溶媒中测定体重和粪便胆汁酸排泄， 致癌物处理的动物。 从致癌作用研究和生物化学 通过研究，有可能确定一种机制， 致癌因素（硒、维生素E、SFA和PUFA）影响致癌过程。 在35日龄时，将对各组动物饲喂实验饲料 含有硒、维生素E、SFA和PUFA的各种组合。 在 50日龄时，除溶剂对照组外的所有动物均将接受皮下注射剂量 AOM（29.6 mg/kg体重，单剂量）。 一些动物用不同的食物 饲料将用于测定上述生化指标， 参数 其余死亡或被处死的动物， 计划（AOM注射后30-32周）将进行尸检， 各组之间的肿瘤发病率比较。

It has been shown that nutrient deficiencies, excesses and imbalances play an important role in the etiology of colon cancer. However, the modulating effects of most nutrients were studied individually with little regard for interacting effects with other nutrients. It is the primary objective of this proposal to gain new insights on the interaction of selenium, vitamin E, saturated fat (SFA) and polyunsaturated fat (PUFA) in colon carcinogenesis. Specifically, it is proposed to assess the role of dietary excess, adequacy or deficiency of selenium and vitamin E, individually and in combination, on azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats fed the diets containing high and low levels of PUFA and SFA. The effect of these diets on the activities of glutathione peroxidase and glutathione S-transferase in liver and colonic mucosa, on the levels of vitamin E and selenium in plasma and liver, on the composition of microsomal membrane fatty acids in liver and colonic mucosa, on testes weights and on fecal bile acid excretion will be determined in vehicle- and carcinogen-treated animals. From the carcinogenesis study and biochemical study, it is possible to identify a mechanism by which these interactive factors (selenium, vitamin E, SFA and PUFA) affect the carcinogenic process. At 35 days of age, groups of animals will be fed experimental diets containing various combinations of selenium, vitamin E, SFA and PUFA. At 50 days of age, all animals except vehicle controls will be given s.c. dose of AOM (29.6 mg/kg body wt., single dose). Some of the animals fed various diets will be used for the determination of the above-mentioned biochemical parameters. The remainder of the animals which die or are sacrificed as scheduled (30-32 weeks post-AOM injection) will be necropsied and colon tumor incidences compared between the various groups.