Our primary goal has been the elucidation of the reactive metabolite which is responsible for the carcinogenic activity of the environmental contaminant benzo(a)pyrene. The approach taken consists of: 1) Synthesis of all possible primary oxidative metabolites as well as selected secondary oxidative metabolites, 2) study of the metabolism of benzo(a)pyrene with liver microsomes, as well as purified and reconstituted cytochrome P-450 systems with and without epoxide hydrase, 3) tests for inherent mutagenicity of the synthetic metabolites toward bacterial and mammalian cells, 4) elucidation of the roles of the cytochrome P-450 system and epoxide hydrase in potentiating or obliterating the mutagenicity of these metabolites, 5) determination of the carcinogenic activity by topical application and subcutaneous injection for these compounds, 6) determination of the rate and nature of the products formed when reactive metabolites such as arene oxides and diol epoxides react with biopolymers and less complex chemical analogs.