ROLE OF PUFA IN CANCER PREVENTION

多不饱和脂肪酸在预防癌症中的作用

• 批准号: 3190371
• 负责人: SUSAN M FISCHER
• 金额: $ 5.24万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1996-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3190371
• 关键词: DNA replication; arachidonate; cancer prevention; carcinogenesis inhibitor; cell membrane; ceramides; chemical carcinogenesis; chemoprevention; dietary lipid; disease /disorder model; eicosanoids; laboratory mouse; linoleate; marine animal oil; nutrition related neoplasm /cancer; nutrition related tag; omega 3 fatty acid; ornithine decarboxylase; phorbols; prostaglandin E; protein kinase C; radiation sensitivity; saturated fatty acids; skin; superoxides; tumor promoters; ultraviolet radiation; unsaturated fatty acids

Recent work on the effect of dietary lipids on the mouse skin initiaiton-promotion model has produced unexpected results - increasing the corn oil (linoleic acid) and decreasing the saturated fat content in a constant fat diet has an inhibitory effect on tumor yield. Because these data are contrary to that reported for the rat mammary and pancreas models, and because of the human health implications, it is necessary to determine the basis for these observations. We hypothesize that this effect occurs for one of two reasons: (1) saturated fat enhances tumorigenesis in the 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion model or (2) linoleic acid has specific biological activity in the skin. The goal of this proposal therefore is to elucidate, the mechanism(s) by which high corn oil/low saturated fat diets suppress tumor development in the TPA promotion model in SENCAR mice and to determine whether this can be extended to a nonphorbol ester promoter, benzoyl peroxide, and for a physical carcinogenic agent, ultraviolet light Two overall approaches will be taken: (1) determine if it is the saturated fat component that is more important than the polyunsaturated fat content and (2) determine whether linoleic acid or its metabolites alter eicosanoid metabolism, have biological activity and/or whether altering dietary levels affects the barrier function .of the skin and thus penetration of chemical promoters.These approaches will be addressed through the following questions: (1) Do various levels of saturated and polyunsaturated dietary fat alter tumorigenesis using the nonphorbol promoter benzoyl peroxide, or ultraviolet (UV) irradiation? (2) Is it the saturated fat or polyunsaturated fat content that is important? (3) Do the above dietary constructs alter parameters known to be associated with promotion/ carcinogenesis? (4) What is the disposition of linoleic acid (LA) in the epidermis: Is it converted to arachidonic acid (AA)? Does LA or its metabolites affect AA metabolism? What are its metabolic products? (5) Does LA, its metabolites, the monosaturated 18: 1, or the 12:0 and 16:0 saturated fatty acids have biological activity, with regard to several tumor promotion related parameters? (6) Are high or low levels of dietary linoleic acid or saturated fat associated with changes in the barrier function of the skin (ceramides) that could affect the penetration or activity of exogenous chemical tumor promoters?

膳食脂质对小鼠皮肤影响的最新研究 启动-推广模式产生了意想不到的结果-- 增加玉米油(亚油酸)，减少 恒定脂肪饮食中的饱和脂肪含量具有抑制作用 对肿瘤产率的影响。因为这些数据与此相反 关于大鼠乳腺和胰腺模型的报道，以及因为 对人类健康的影响，有必要确定 为这些观察提供了依据。我们假设这一效应 发生这种情况的原因有两个：(1)饱和脂肪有助于 12-O-十四酰佛波醇-13-乙酸酯(TPA)的致瘤作用 促进模型或(2)亚油酸具有特定的生物学特性 皮肤中的活动。因此，这项提议的目标是 阐明高玉米油/低饱和度的机理(S) 在TPA促进模型中，脂肪饮食抑制肿瘤发展 并确定这是否可以扩展到Sencar小鼠 非佛波酯促进剂过氧化苯甲酰，并用于物理 致癌剂、紫外线两个整体途径将 服用：(1)确定是不是饱和脂肪成分 比多不饱和脂肪含量更重要，(2) 测定亚油酸或其代谢物是否改变 二十烷类代谢，具有生物活性和/或 改变饮食水平会影响皮肤的屏障功能 因此化学促进剂的渗透。这些方法将 通过以下问题得到解决：(1)做各种 饱和和多不饱和膳食脂肪水平变化 使用非佛波醇启动子过氧化苯甲酰的肿瘤形成，或 紫外线(UV)照射？(2)是饱和脂肪还是 多不饱和脂肪含量重要吗？(3)做到以上几点 饮食结构改变了已知与以下因素相关的参数 促进/致癌？(4)什么是处置 表皮中的亚油酸(LA)：它是否转化为 花生四烯酸(AA)？LA或其代谢物影响AA吗？ 新陈代谢？它的代谢产物是什么？洛杉矶，它的 代谢物，单饱和度为18：1或12：0和16：0 饱和脂肪酸在以下方面具有生物活性 与肿瘤促进相关的几个参数？(6)是高还是低 饮食中的亚油酸或饱和脂肪水平与 皮肤(神经酰胺)屏障功能的变化 可能会影响外源化学物质的渗透或活性 肿瘤促进剂？