Although a vast amount of research activities have been directed toward the role of dietary fat in growth of the carcinomatous rodent mammary gland, it is now important to determine whether or not carcinomatous human breast tissues respond to dietary fat as has been amply demonstrated in rodents. Although numerous epidemiological studies in human populations have provided evidence that diets rich in fat may increase the risk for the development of breast cancer, a number of more recent studies have seriously questioned this relationship. Thus, to date, we have only epidemiological data to link dietary fat and human breast cancerigenesis. In this research proposal, we intend to examine this potentially important relationship by determining whether or not dietary fat can affect growth processes of carcinomatous human breast epithelial cells maintained in female athymic nude mice. More specifically, the following four objectives will be pursued. 1.Can the amount and type of dietary fat affect the growth of carcinomatous human breast cells (hormone responsiveness MCF-7, T47-D, ZR75-1 cell lines, hormone nonresponsive Hs578T, MX-1 cell lines)? 2.Is the stimulatory effect of a high fat diet on growth of carcinomatous human breast cells contingent upon an ad libitum type of feeding pattern? 3.Is the inhibitory effect of a fish oil diet on growth of carcinomatous human breast cells a function of increased accumulation of carcinoma lipid peroxides? 4.Does the amount and type of dietary fat effect the growth of carcinomatous human breast cells by altering carcinoma cell proliferation and/or by altering carcinoma cell loss (cytolysis)? In summary, we feel that the research projects outlined in this research proposal are a logical and important extension of our past studies; these studies are not only of conceptual and of mechanistic importance but, in addition, address an important current practical issue.
