NMU INDUCED MAMMARY CANCER AND OMEGA 3 FATTY ACIDS

NMU 诱发乳腺癌和 Omega 3 脂肪酸

• 批准号: 3190883
• 负责人: LEONARD A COHEN
• 金额: $ 10.2万
• 依托单位: INSTITUTE FOR CANCER PREVENTION
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3190883
• 关键词: blood lipid; breast neoplasms; carcinogenesis inhibitor; chemical carcinogenesis; disease /disorder model; hormone receptor; laboratory rat; lipid biosynthesis; nitrosourea; nutrition aspect of cancer; nutrition related neoplasm /cancer; nutrition related tag; omega 3 fatty acid; phosphatidylcholines; phosphatidylethanolamines; phosphatidylinositols; phosphatidylserines; phospholipids; prolactin; tumor promoters; vegetable oils

The purpose of this study is to determine the role played by omega-3 fatty acids in mammary carcinogenesis. The N- nitrosomethylurea-(MNU)- induced rat mammary tumor will serve as a model for human breast cancer. The experimental diets are designed such that the ratio of omega-6/omega-3 fatty acids will vary form 7:1 to 2:1 and 0.7:1. (The ratio in the contemporary Western diet is approximately 10:1). The experimental diets will be fed at 23% (wt/wt), which approximates the current U.S. fat intake. High-fat (HF) and low-fat (LF) corn oil (23% and 5%, respectively) will serve as internal controls. If the balance of omega-6/omega-3 fatty acids plays a determining role in mammary tumor development, then tumor incidence should approach that of the LF corn oil group as omega-3 levels increase; if, on the other hand omega-3 fatty acids have effects similar to omega-6 fatty acids, then tumor incidences should remain in the HF corn oil range. The experimental protocols are designed to test the effects of omega-3 fatty acids on (a) the initiation phase, (b) the promotion phase, and (c) both the initiation and promotion phases. In this way, the stage in carcinogenesis at which the optimal chemopreventive effects of omega-3 fatty acids are exerted can be determined. Such information is important, both theoretically and in the design of dietary intervention trials. Evidence suggest that omega-3 fatty acids compete with omega-6 fatty acids for common metabolic pathways. As a result omega-3 fatty acids may replace omega-6 fatty acids in cell membranes, thereby altering the structural and functional integrity of the membrane. Since diet has been shown to alter serum prolactin levels and prolactin receptor status, we propose to test the hypothesis that the tumor-inhibiting effects of omega-3 diets may be exerted via changes in membrane-bound prolactin receptors and/or changes in circulating levels of prolactin, a known tumor promoter. To test this hypothesis, the fatty acid composition of (a) serum neutral and phospholipids and (b) tumor neutral lipids and the four new major subclasses of phospholipids, namely, phosphatidyl choline, phosphatidyl inositol, phosphatidyl serine and phosphatidyl ethanolamine will be determined. In addition, both immunoassayable and bioassayable serum prolactin and tumor prolactin receptor content will be assessed in each treatment group. The ultimate objective of this proposal is the development of an optimal omega-6/omega-3 dietary fatty acid balance for the primary and secondary prevention of breast cancer in high-risk countries, such as the U.S.A.

这项研究的目的是确定所发挥的作用， ω-3脂肪酸在乳腺癌发生中的作用 N- 亚硝基甲基脲（MNU）诱导的大鼠乳腺肿瘤将有助于 作为人类乳腺癌的模型。 实验饮食是 设计成使得ω-6/ω-3脂肪酸的比例将 从7：1变化到2：1和0.7：1。 (The当代比率 西方饮食约为10：1）。 实验饮食将 以23%（wt/wt）的比例饲喂，这接近目前美国的脂肪含量。 摄入 高脂肪（HF）和低脂肪（LF）玉米油（23%和5%， 将作为内部控制。 如果余额 omega-6/omega-3脂肪酸在以下方面起着决定性作用： 乳腺肿瘤的发展，那么肿瘤的发病率应该 随着omega-3水平的增加，接近LF玉米油组; 另一方面，如果ω-3脂肪酸具有类似于 omega-6脂肪酸，那么肿瘤发病率应该保持在 HF玉米油系列。 实验方案的目的是测试的影响， ω-3脂肪酸对（a）起始阶段，（B）促进 阶段，以及（c）启动和促进阶段。 在这 在癌症发生的最佳阶段， ω-3脂肪酸的化学预防作用可以 被确定。 这些信息在理论上是重要的， 以及饮食干预试验的设计。 证据表明 omega-3脂肪酸与omega-6脂肪酸竞争， 共同的代谢途径。 因此，ω-3脂肪酸 可以取代细胞膜中的omega-6脂肪酸， 改变膜的结构和功能完整性。 由于饮食已被证明可以改变血清催乳素水平， 催乳素受体状态，我们建议测试的假设， omega-3饮食的肿瘤抑制作用可以通过以下方式发挥 膜结合催乳素受体的变化和/或 催乳素的循环水平，一种已知的肿瘤促进剂。 测试 这一假设，（a）血清中性脂肪酸组成 和磷脂和（B）肿瘤中性脂质和四种新的 磷脂的主要亚类，即磷脂酰胆碱， 磷脂酰肌醇、磷脂酰丝氨酸和磷脂酰 乙醇胺将被确定。 此外， 血清催乳素与肿瘤 将在每次治疗中评估催乳素受体含量 组 这项建议的最终目标是制定一项 最佳的omega-6/omega-3膳食脂肪酸平衡， 高危人群乳腺癌的一级和二级预防 国家，如美国。