We propose to use the polyoma virus-mouse system to investigate aspects of virus-host interactions leading to induction of tumors. Two areas of general relevance to the biology of cancer will be investigated. The first concerns the apparent inability of polyoma virus to block the actions of p53, raising questions of the role of genomic instability in driving tumor development in this system. This will be approached using molecular cytogenetic techniques to study genomic changes in polyoma-induced mouse tumors, studies in tissue culture to determine how the virus may override or bypass p53, and derivation of transgenic mice expressing regulatable polyoma T (tumor) antigens. The second area concerns the roles of the host genetic background in determining patterns of susceptibility and resistance to tumors. Three mouse strains exhibiting different tumor responses will be studied - 1) susceptibility to tumor induction based on failure to develop tumor immunity, 2) tissue specific resistance to mammary tumors, and 3) propensity of bone tumors to metastasize to the lung. Genetic and physiological approaches will be used in attempts to understand the bases of these host phenotypes.
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