CAN DIETARY FAT--MAMMARY GLAND GROWTH PROCESSES

越来越多的流行病学证据表明，人类体内高水平的

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.