CAN DIETARY FAT--MAMMARY GLAND GROWTH PROCESSES

膳食脂肪罐头——乳腺生长过程

• 批准号: 3184531
• 负责人: CLIFFORD W WELSCH
• 金额: $ 7.01万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3184531
• 关键词: autoradiography; breast neoplasms; computed axial tomography; dietary lipid; disease /disorder model; image processing; laboratory mouse; magnetic resonance imaging; mammary gland; neoplastic growth; nutrition related neoplasm /cancer; nutrition related tag; tissue /cell culture

There is increasing epidemiological evidence in humans that high levels of dietary fat may increase the incidence of cancer in a number of organ sites, in particular, the breast, prostate and colon. In a wide variety of experimental animal models for human breast cancer, it is quite apparent that hyperalimentation of fat enhances mammary gland tumorigenesis, i.e., the incidence of mammary carcinomas is increased in experimental animals fed high levels of dietary fat. Not only is the quantity of fat important, but the type of fat also markedly influences this neoplastic process. In general, most vegetable fats, (most of which have high levels of unsaturated fatty acids) are substantially more efficacious than animal meat fats (rich in saturated fatty acids) in the enhancement of experimental animal mammary gland tumorigenesis. In contrast, fish oils (rich in polyunsaturated fatty acids), when fed in large amounts, do not appear to enhance mammary gland tumorigenesis in experimental animal models. The mechanism(s) by which certain high fat diets enhance mammary gland tumorigenesis is unknown. We are asking two very fundamental questions. One, can hyperalimentation of fat affect developmental growth processes of the normal mammary gland? Two, can the type of fat influence this important process? To date, we do not know the answer to either one of these important and essential questions. To answer these questions, we will determine the comparative mammae growth promoting activities of hyperalimentation of three major classes of fat, i.e., vegetable fats (corn oil, olive oil, coconut oil), animal meat fats (lard, beef tallow) and a fish fat (Menhaden oil). Each of these fats differ widely in their fatty acid composition and are representative of the wide range of fats consumed by human populations. Importantly, each one of these fats also differ substantially in their ability to enhance mammary gland tumorigenesis in experimental animals. Mammae growth processes will be assessed in female Balb/c mice; mammary growth, as a function of diet, will be determined in vivo in normal cycling mice and in mice treated with mammogenic hormones. Mammae hormone induced growth responsiveness, as a function of diet, will also be determined in short term organ culture analysis. Quantification of mammary gland growth will be enacted by (1) morphological wholemount evaluation, (2) epithelial area analysis via computer image analysis and (3) epithelial DNA synthesis via 3H-thymidine autoradiographic analysis.

越来越多的流行病学证据表明， 饮食中的脂肪可能会增加许多器官癌症的发病率 特别是乳腺、前列腺和结肠。 以各种各样的 作为人类乳腺癌的实验动物模型， 脂肪的高营养增强了乳腺肿瘤的发生，即， 实验动物乳腺癌的发病率增加 吃高脂肪食物 不仅脂肪的数量很重要， 但脂肪的类型也明显影响这种肿瘤过程。 在 一般来说，大多数植物脂肪（其中大多数具有高水平的 不饱和脂肪酸）实质上比动物的更有效 肉类脂肪（富含饱和脂肪酸）， 实验动物乳腺肿瘤发生。 相反，鱼油 (rich多不饱和脂肪酸），当大量喂食时， 在实验动物中似乎增强乳腺肿瘤发生 模型 某些高脂肪饮食增强乳腺癌的机制 腺体肿瘤发生是未知的。 我们在问两个非常基本的问题。 第一，高营养 影响正常乳腺的发育生长过程？ 二、脂肪的种类会影响这一重要过程吗？ 到目前为止， 我不知道这些重要和基本问题的答案 问题. 为了回答这些问题，我们将确定比较 三种主要营养素的高营养促进乳房生长的活性 脂肪的种类，即，植物脂肪（玉米油、橄榄油、椰子油）， 动物肉脂肪（猪油、牛脂）和鱼脂肪（鲱鱼油）。 每个 这些脂肪的脂肪酸组成差异很大， 代表了人类消费的广泛脂肪。 重要的是，这些脂肪中的每一种在其 增强实验动物乳腺肿瘤发生的能力。 将在雌性Balb/c小鼠中评估哺乳动物生长过程; 生长作为饮食的函数，将在正常循环中在体内测定 小鼠和用促乳腺激素治疗的小鼠中。 乳腺激素诱导 生长反应性作为饮食的函数，也将在 短期器官培养分析。 乳腺生长的定量 将通过（1）形态学整体评价，（2）上皮 通过计算机图像分析的面积分析和（3）上皮DNA合成 通过3 H-胸苷放射自显影分析。