ROLE OF OMEGA-3 PUFA IN CANCER PREVENTION

OMEGA-3 多不饱和脂肪酸在预防癌症中的作用

• 批准号: 3190365
• 负责人: SUSAN M FISCHER
• 金额: $ 13.65万
• 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 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3190365
• 关键词: antibody dependent killer cell; arachidonate; benzanthracenes; benzoates; cancer prevention; carcinogenesis inhibitor; cell differentiation; cell growth regulation; chemical binding; chemical carcinogen; chemical carcinogenesis; delayed hypersensitivity; fatty acid metabolism; inflammation; laboratory mouse; mitogens; mixed lymphocyte reaction test; nitrosoguanidines; nutrient drug interaction; nutrient intake activity; nutrition aspect of cancer; nutrition related neoplasm /cancer; nutrition related tag; omega 3 fatty acid; ornithine decarboxylase; phorbols; protein glutamine gamma glutamyltransferase; skin neoplasms; toxin metabolism; tumor promoters

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.

这项调查的目标是确定 与n-6-脂肪酸相比，高n-3脂肪酸的等卡路里饮食将有 银杏叶提取物对小鼠皮肤癌变的化学预防作用 减少肿瘤的发生和促进。这将是确定的 无论是含10%脂肪的等卡路里饮食是高n-6，n- 3、两种或以饱和脂肪酸为主的脂肪酸会改变肿瘤 对需要新陈代谢的致癌物的反应，7，12- 二甲基苯并(A)菲(DMBA)和一种直接致癌物质， N-甲基-N-硝基-N-亚硝胺(MNNG)。饮食影响 致癌物与DNA的结合及其代谢物的研究 表皮也将被测量。这些饮食的效果将 也是关于肿瘤促进的研究，使用12-0- 十四醇-13-乙酸酯(TPA)和过氧化苯甲酰，AS 以及几个被认为对 促进过程：增殖、炎症和鸟氨酸 脱羧酶诱导。因为预计高n-6脂肪 酸性饮食将增强促进作用，将进行肿瘤实验 其中主要的花生四烯酸代谢物应用于小鼠 关于高n-3脂肪酸饮食部分恢复的尝试 升职。还将进行研究，以确定是否 上面看到的脂肪酸效应是源于表皮，而不是 而不是由于免疫等系统参数的变化 系统。这将通过将小鼠表皮细胞培养在 含有n-6和/或n-3脂肪酸和 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是否 影响免疫系统对挑战的反应能力。 将测量几个参数：迟发性超敏反应， 有丝分裂原反应性、混合淋巴细胞反应和自然 杀手细胞的活动。