PUFA AND CANCER PREVENTION

膳食脂质对小鼠皮肤影响的研究进展 “先启后促”的模式产生了意想不到的效果-- 增加玉米油（亚油酸）和减少 饱和脂肪含量在恒定的脂肪饮食具有抑制作用， 对肿瘤产量的影响 因为这些数据与此相反 报告了大鼠乳腺和胰腺模型，由于 对人类健康的影响，有必要确定 这些观察的基础。 我们假设这种效应 发生的原因有两个：（1）饱和脂肪增强 12-O-十四酰佛波醇-13-乙酸酯（TPA）的肿瘤发生 促进模型或（2）亚油酸具有特定的生物学活性 皮肤中的活动。 因此，本提案的目标是 阐明高玉米油/低饱和玉米油 在TPA促进模型中脂肪饮食抑制肿瘤发展 在SENCAR小鼠中，并确定这是否可以扩展到 非佛波醇酯促进剂，过氧化苯甲酰，和用于物理 致癌物质，紫外线两种总体方法将 （1）确定是否是饱和脂肪成分， 比多不饱和脂肪含量更重要;（2） 确定亚油酸或其代谢产物是否改变 类二十烷酸代谢，具有生物活性和/或是否 改变饮食水平会影响皮肤的屏障功能 从而渗透化学促进剂。这些方法将 通过以下问题来解决：（1）各种 饱和和多不饱和膳食脂肪的水平会改变 使用非佛波醇促进剂过氧化苯甲酰的肿瘤发生，或 紫外线照射(2)是饱和脂肪还是 多不饱和脂肪含量重要吗？(3)做到以上 饮食结构改变了已知与 促进/致癌作用？(4)这是什么意思？ 表皮中的亚油酸（LA）：它是否转化为 花生四烯酸（AA）？LA或其代谢产物是否影响AA 新陈代谢？它的代谢产物是什么？(5)洛杉矶，它的 代谢物，单饱和18：1，或12：0和16：0 饱和脂肪酸具有生物活性， 几个肿瘤促进相关参数？(6)有高有低 饮食中亚油酸或饱和脂肪的水平与 皮肤屏障功能的变化（神经酰胺）， 可能影响外源性化学物质的渗透或活性 肿瘤促进剂？

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?