Our long-range goal is to understand how dietary modulation changes the incidence of murine mammary tumorigenesis. Our studies during the last three years have revealed that low-calorie low-fat diet reduces the development of preneoplastic lesions (HANs), the incidence of mammary tumors, the amount of circulating serum prolactin, anti-MuMTV antibody and the production of murine mammary tumor virus (MuMTV) in high-mammary-tumor-incidence C3H mice. We have also found that a low-calorie high-fat diet results in a high tumor incidence in these mice. On the basis of these findings, we now propose to quantify the expression of MuMTV RNA and proteins in the mammary glands of mice fed a low-fat high-calorie an a low-fat low-calories diet. In order to determine which of the various factors that may profoundly influence mammary tumor development, we will determine the effect of low-calories high-fat diet on the development of HANs, the expression of MuMTV-RNA, -proteins and virus particles in the mammary glands and measure the levels of circulating serum prolactin in these mice. We will also determine the fatty acid composition of, and prostaglandin production by, mammary glands and mammary tumors of mice fed a low-calorie low-fat and a low-calorie high-fat diet. We propose to determine if the mammary tumor incidence, HAN development, MuMTV production, prostaglandin synthesis or the fatty acid composition of the mammary glands of C3H mice fed low-calorie high-fat or low-calorie low-fat diets can be altered by lowering or raising the serum prolactin levels using drugs or pituitary isografts. In our studies we will use histological methods to quantitate HAN development, electron microscopy to evaluate the production of MuMTV particles, molecular hybridization for MuMTV-RNA quantitation, radioimmunoassays to quantify serum prolactin and MuMTV proteins, and high pressure liquid chromatography to evaluate fatty acid composition and prostaglandin production. As a result of our proposed studies, we hope to understand the effect of dietary intake on the complex interaction between hormones, fatty acids, prostaglandins and MuMTV, and how this interaction influences mammary tumorigenesis in mice.
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