NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals.

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Abstract
With NADPH as the electron donor, rat liver NADPH cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4) catalyzes the single-electron reduction of several quinone antibiotics to a semiquinone or free radical state. The benzanthraquinones adriamycin, daunorubicin, carminomycin, 7-O-methylnogalarol and aclacinomycin A and the N-heterocyclic quinones streptonigrin and mitomycin C are activated to free radical intermediates which can transfer their single electron to O2 to form superoxide. The overall Km range for this electron transfer is 0.4 to 42.1 .times. 10-4 M. The formation of the site-specific free radical intermediate is probably central to the cytotoxic action of these antibiotics.