THE ROLE OF OMEGA-3 PUFA IN CANCER PREVENTION

本次调查的目的是确定 相对于n-6-脂肪酸，n-3含量高的等热量饮食将具有 对小鼠皮肤癌变化学预防作用 减少肿瘤的发生和发展。将确定 无论是高n-6，n- 3、两种或主要是饱和脂肪酸改变肿瘤 对需要代谢的致癌物的反应，7，12- 二甲基苯并（a）蒽（DMBA）和一种直接致癌物， N-甲基-N-硝基-N-亚硝基胍（MNNG）。 饮食影响 致癌物与DNA的结合以及 还将测量表皮。 这些饮食的效果将 也可以使用12-0- 十四烷基佛波醇-13-乙酸酯（TPA）和过氧化苯甲酰， 以及几个参数被认为是重要的， 促进过程：增生、炎症和鸟氨酸 脱羧酶诱导 因为预计高n-6脂肪 酸性饮食将促进促进肿瘤实验 其中将主要的花生四烯酸代谢物应用于小鼠， 高n-3脂肪酸饮食，试图部分恢复 推广. 还将进行研究，以确定是否 上面看到的脂肪酸效应是表皮起源的， 而不是由于系统参数的变化，如免疫 系统 这将通过将小鼠表皮细胞培养在 含有n-6和/或n-3脂肪酸的成分确定的培养基， 测量生长和分化的几个参数。 最后，还将确定不同的脂肪酸饮食 影响免疫系统对攻击的反应。 将测量几个参数：迟发型超敏反应， 有丝分裂原反应、混合淋巴细胞反应和自然 杀伤细胞活性

The goals of this investigation are to determine whether isocaloric diets high in n-3 relative to n-6-fatty acids will have the chemopreventive effect in mouse skin carcainogenesis of reducing tumor initiation and promotion. It will be determined whether isocaloric diets containing 10% fat as either high n-6, n- 3, both or predominately saturated fatty acids alter tumor response to a metabolism-requiring carcinogen, 7,12- dimethylbenz(a)anthrene (DMBA) and a direct acting carcinogen, N-methyl-N-nitro-N-nitrosoquanidine (MNNG). Dietary effects on carcinogen binding to DNA and metabolite profiles in the epidermis will also be measured. The effect of these diets will also be studied with respect to tumor promotion, using 12-0- tetradecanyolphorbol-13-acetate (TPA) and benzoyl peroxide, as well as several parameters believed to be important to the promotion process: hyperplasia, inflammation and ornithine decarboxylase induction. Since it is expected that high n-6 fatty acid diets will enhance promotion, tumor experiments will be done in which the major arachidonate metabolites are applied to mice on the high n-3 fatty acid diets to attempt to partially restore promotion. Studies will also be carried out to determine whether the fatty acid effects seen above are epidermal in origin rather than due to changes in systemic parameters such as the immune system. This will be done by culturing mouse epidermal cells in a defined medium containing n-6 and/or n-3 fatty acids and measuring several parameters of growth and differentiation. Finally, it will also be determined if the different fatty acid diets affect the responsiveness of the immune system to challenge. Several parameters will be measured: delayed hypersensitivity, mitogen responsiveness, mixed lymphocyte reactions and natural killer cell activity.