Involvement of mammary tumor viruses and mammotropic hormones in mouse mammary carcinogenesis is currently understood only in terms of poorly defined influences. Our studies will focus on the resolution of roles for endogenous MuMTV and mammotropic hormones in etiology of neoplastic transformation of mouse mammary epithelial cells. Roles for these agents will be resolved in a cell culture system. In this system, we can precisely control the hormonal environment of cells; we can use homogeneous populations of normal or neoplastic phenotypes and we can perform kinetics experiments to the level of refinement necessary to establish temporal relationships between virus and cell specific events. Markers will be established for hyperplastic and malignant mammary epithelial cells based on different structural and functional alterations characteristic of the neoplastic state. Sensitive detection methods are available for MuMTV group specific antigens and genome RNA. Using the virus and cell markers, we will determine if when endogenous MuMTV is chemically induced in normal cells, transformation occurs; if hormones transform cells and, if so, are MuMTV genes expressed enroute to transformation.