TYPES AND AMOUNT OF DIETARY FAT AND COLON CANCER

流行病学和动物模型研究表明，饮食摄入量 某些类型的脂肪在结肠癌风险中起作用 发展。长期的目标是理解调制 脂肪的数量和种类对脂肪酸组成的影响 在结肠癌的促进和进展中起重要作用。具体地说，建议 探讨膳食脂肪种类和数量的作用机制(S) 作为玉米油(CO)和富含omega-6和omega-3的人造鱼油(FO) 脂肪酸和混合脂分别在饱和脂肪中含量较高。 最近的研究表明，某些饮食脂肪的高摄入量 与次级胆汁产生的改变有关 结肠内容物中的酸、二酰甘油和脂肪酸 它可以进入结肠粘膜并激活几个细胞 事件包括蛋白激酶C(PKC)，花生四烯酸代谢和 RAS p21，仅举几例。这些生化和分子事件导致 以膳食脂肪的种类和数量为基础进行深入研究 学习。具体地说，建议确定饮食的效果 高CO、低CO、高FO和混合脂的生产 DAG肠道微生物区系、结肠腔脂肪酸组成的研究 (粪便)DAGs，结肠粘膜和肿瘤上调和下调- 蛋白激酶C同工酶、环氧合酶同工酶和法尼基的调节 结肠促进和进展期的蛋白转移酶 致癌。在5周龄时，雄性F344组大鼠将被喂养 含CO(LFCO)的低脂AIN-76A日粮。在7周龄时， 每周接受两次S.C.治疗。偶氮甲烷的剂量 (AOM)或生理盐水(车辆)，一天后，他们将被 转移到含有CO(HFCO)或FO(HFF0)的高脂肪饮食中。一 组将继续进行LFCO饮食。然后成群的动物就会 分别于AOM或生理盐水处理后1、12、36、50周处死动物。 祭祀前，每天采集一周的粪便样本。 并分析粪便中的DAG质量和它们的脂肪酸 组成。盲肠内容物将用于确定生产 肠道菌群对DAG的影响。分别于第1、12、12周采集结肠粘膜。 36和50以及结肠肿瘤将被用来确定 PKC、环氧合酶1和2、法尼基蛋白转移酶。这些 AOM或AOM对动物生化和分子参数的影响 生理盐水和饲喂实验饲料将进行统计分析 确定差异的重要性。希望这一结果 由拟议的机械论研究产生的结果将加强 结肠癌一级预防和二级预防的理论基础 饮食调节。

Epidemiologic and animal model studies suggest that dietary intake of certain types of fat plays a role in the risk of colon cancer development. The long term objective is to understand the modulating effects of amount and types of fat differing in fatty acid composition in colon tumor promotion and progression. Specifically, it is proposed to investigate the mechanism(s) of types and amount of dietary fat such as corn oil (CO) and menhaden fish oil (FO) rich in omega-6 and omega-3 fatty acids, respectively and mixed lipid high in saturated fats. Recent studies indicate that high intake of certain dietary fats has been associated with an alteration in the production of secondary bile acids, diacylglycerols (DAG) and fatty acids in the colonic contents which could enter the colonic mucosa and activate several cellular events including protein kinase C (PKC), arachidonic acid metabolism and ras p21, to cite a few. These biochemical and molecular events induced by types and amount of dietary fat became a basis to conduct in-depth studies. Specifically, it is proposed to determine the effect of diets high and low in CO and high in FO and mixed lipids on the production of DAG by the gut microflora, fatty acid composition of colonic luminal (fecal) DAGs, colonic mucosal and tumor up-regulation and down- regulation of PKC isozymes, cyclooxygenase isozymes, and farnesyl protein transferase during promotion and progression stages of colon carcinogenesis. At 5 weeks of age, groups of male F344 rats will be fed low-fat AIN-76A diet containing CO (LFCO). At 7 weeks of age, groups of animals will be treated with two weekly s.c. doses of azoxymethane (AOM) or normal saline (vehicle and one day later, they will be transferred to high fat diets containing CO (HFCO) or FO (HFF0). One group will be continued on LFCO diet. Then the groups of animals will be sacrificed at weeks 1, 12, 36 and 50 after AOM or saline treatment. Prior to sacrifice, daily stool samples for one week will be collected from each animal and analyzed for fecal DAG mass and their fatty acid composition. Cecal contents will be used to determine the production of DAG by intestinal microflora. Colon mucosa harvested at weeks 1, 12, 36 and 50 and colon tumors will be used to determine the isoforms of PKC, cyclooxygenase 1 and 2, and farnesyl-protein transferase. These biochemical and molecular parameters of animals treated with AOM or saline and fed the experimental diets will be analyzed statistically to determine the significance of difference. It is hoped that the results generated from the proposed mechanistic study will strengthen the rationale for primary and secondary prevention of colon cancer through dietary modulation.