The major objective of this proposal is to study the promoting effect of dietary fat on mammary carcinogenesis.
Specific aims i nclude the following. (1) The effect of quantity and type of fat on mammary carcinogenesis induce by dimethylbenz(a) anthracene (DMBA) will be examined in female rats. In these experiments, saturated and unsaturated fat will be compared with a blend of fat simulating that found in the typical American diet. Results of this study will be most relevant to nutritionists and oncologists in their deliberations to recommend a reduction of fat intake to lower the risk of breast cancer. More importantly, these results will specifically indicate how much the fat content of the diet needs to be reduced or conversely, if anything meaningful is to be gained by only a small reduction. (2) The efficacy of dietary fat inpromoting mammary carcinogenesis at various times after the administration of DMBA will be examined to determine whether rats switched to a high fat diet several months after the administration of DMBA still develop a high incidence of tumors. (3) The effect of trans fatty acids (produced during hydrogenation in the processing of vegetable oil) on DMBA-induced mammary carcinogenesis will be studied in female rats. (4) The effect of both quantity and type of dietary fat on the DNA synthetic rate of the mammary gland will be examined by measuring the incorporation of 3H-thymidine into the DNA of isolated epithelial cells at various times after the administration of DMBA. The purpose of this experiment will be to determine if there is a correlation between the promoting effect of dietary fat on mammary carcinogenesis and an effect of fat on the DNA synthetic rate of the mammary gland. (5) The effect of quantity and type of dietary fat will be examined in rats bearing transplantable metastasing mammary tumors to determine if fat affects either the extent or the location of metastases. (6) The effect of dietary fat on the development and progression of ductal hyperplasia will be examined in the mammary gland of DMBA-treated mice. In view of the overwhelming epidmiological and experimental evidence liking dietary fat and breast cancer, it is felt that further research focused on defining the conditions under which fat is most effective in stimulating mammary neoplasia should be an area of high priority towards realizing our goal of reducing breast cancer morbidity.
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