NMU INDUCED MAMMARY CANCER AND OMEGA 3 FATTY ACIDS

这项研究的目的是确定 Omega-3脂肪酸在乳腺癌发生中的作用这个N- 亚硝基甲基脲(MNU)诱导的大鼠乳腺肿瘤将服务于 作为人类乳腺癌的模型。试验性的饮食是 设计使得omega-6/omega-3脂肪酸的比率将 从7：1到2：1和0.7：1。(当代 西式饮食约为10：1)。试验性的饮食将 以23%(wt/wt)的比例喂食，这接近目前美国的脂肪 入口处。高脂(HF)和低脂(LF)玉米油(23%和5%， 分别)将作为内部控制。如果剩余的资金 Omega-6/omega-3脂肪酸在 乳腺肿瘤的发生，那么肿瘤的发病率应该 随着omega-3水平的升高，接近LF玉米油组的水平； 另一方面，如果omega-3脂肪酸具有类似于 欧米茄-6脂肪酸，那么肿瘤的发病率应该保持在 HF玉米油系列。 实验方案的设计是为了测试 欧米茄-3脂肪酸在(A)启动阶段，(B)促进 (C)启动阶段和推广阶段。在这 方式，在癌变的阶段，最佳 欧米茄-3脂肪酸的化学预防作用可以 要下定决心。这些信息在理论上都很重要 以及饮食干预试验的设计。有证据表明 Omega-3脂肪酸与omega-6脂肪酸竞争 常见的代谢途径。其结果是omega-3脂肪酸 可以取代细胞膜中的omega-6脂肪酸，从而 改变膜的结构和功能的完整性。 由于饮食已被证明可以改变血清催乳素水平和 催乳素受体状态，我们建议检验这一假设 Omega-3饮食的抑瘤作用可能是通过 膜结合催乳素受体的变化和/或 已知的肿瘤促进剂催乳素的循环水平。为了测试 这一假设认为，(A)血清中的脂肪酸组成为中性 和磷脂和(B)肿瘤中性脂和四种新的 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肌醇 乙醇胺将被测定。此外，两者 血清催乳素免疫测定和生物测定与肿瘤 将在每种治疗中评估催乳素受体的含量 一群人。 这项建议的最终目标是开发一种 膳食中omega-6/omega-3的最佳脂肪酸平衡 高危人群乳腺癌的一级预防和二级预防 国家，如美国。

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.