Our overall goal is to delineate the mechanism(s) whereby dietary polyunsaturated fatty acids increase the size of mammary adenocarcinomas. The mouse mammary gland-tumor system will be used as the model, since four distinct stages of tumorigenesis are easily identifiable; (a) normal epithelial cells; (b) transformation of normal cells into """"""""inapparent"""""""" transformed cells (initiation); (c) expression of the inapparent transformed cells as preneoplastic hyperplastic alveolar nodules (HAN); and (d) transformation of HAN into frank adenocarcinoma. The BALB/c mouse, a strain which is virus-free, will be used in studies with normal tissue and the BALB/cfC3H mouse, high mammary tumor incidence strain infected with the mammary tumor virus, will be used to study the effects of dietary linoleate on the incidence and expression of the inapparent transformed cells. Various HAN lines of different growth rates and tumor potentials will also be studied. Dietary polyunsaturated fat does not increase the growth rate of HAN, but only of normal and tumor tissue. Studies designed to understand this phenomenon will be conducted. During the previous grant period we showed that the size of transplantable tumors was not increased by an increase in the numbers of host inflammatory cells nor by an increase in cell proliferation but by a decrease in the rate of tumor cell loss. The role of tumor-associated lymphocytes in this latter process will be explored. The involvements of specific prostaglandins in the tumor-host inflammatory cell interaction and their relationship to fat-enhance tumor growth will also be investigated. The techniques used will include cell dissociation and implantation of such cells into cleared mammary fat pads, serial propagation of HAN, Winn assays, cell culture, prostaglandin assays, as well as other methods commonly associated with immunology, enzymology, and tumor biology.
