This application proposes to continue studies on the enzymic activation of environmental toxins; in particular, certain aspects of the biochemistry, immunology, and mechanism of action of the liver microsomal enzymes cytochrome P-450 (P-450), NADPH-cytochrome P-450 reductase, and epoxide hydratase. Specific objectives are enumerated below: (1) Characterization of epichlorohydrin adducts and elucidation of roles of glutathione transferases and epoxide hydratases in detoxification. (2) Examination of direct P-450 oxygenation of halogens and the role of glutathione in alkyl halide activation. (3) Study of interaction of P-450 and its reductase, including reductase contribution to P-450 substrate selectivity and possible differential affinities of different P-450s for a common reductase. (4) Immunohistochemical localization of various P-450s in liver, lung, kidney, and other rat tissues. (5) Hydrodynamic characterization of the behavior of epoxide hydratase in solution, including complexation of the enzyme with P-450s and NADPPH-cytochrome P-450 reductase. (6) Identification and comparison of the sites of epoxide hydratase involved in catalysis, regulation, and antibody binding. (7) Physico-chemical studies of P-450s: a) identification of common antigenic sites among various P-450s, b) modification of individual residues to determine which are involved in substrate specificity, and c) enzyme immobilization to facilitate use of P-450s in synthetic work. (8) Correlation of de novo enzyme synthesis with induction of P-450 and epoxide hydratase activities in cultured cells.