Benzo[a]pyrene dione‐benzo[a]pyrene diol oxidation‐reduction couples; involvement in DNA damage, cellular toxicity, and carcinogenesis

Three isomeric quinone metabolites of the environmental carcinogen benzo[a]pyrene undergo reversible, univalent oxidation‐reduction cycles involving the corresponding benzo[a]pyrene diols and intermediate semiquinone radicals. Under aner‐obic conditions, benzo[a]pyrene 1,6‐dione, benzo[a]pyrene 3,6‐dione, and benzo[a]pyrene 6,12‐dione are readily reduced by mild biological agents such as NADH and glutathione. The benzo[a]pyrene diols, in turn, are very rapidly autooxidized to diones when exposed to air. Substantial amounts of hydrogen peroxide are produced during these autooxidations. The benzo[a]pyrene diol/benzo[a]pyrene dione interconversions proceed by one‐electron steps; the corresponding semiquinone radicals were detected as intermediates when the reactions were carried out at high pH. Benzo[a]pyrene diones are electron‐acceptor substrates for NADH dehy‐drogenase. Catalytic amounts of these metabolites, together with this respiratory enzyme, function as cyclic oxidation‐reduction couples to link NAD...