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  • Title: NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals.
    Author: Bachur NR, Gordon SL, Gee MV, Kon H.
    Journal: Proc Natl Acad Sci U S A; 1979 Feb; 76(2):954-7. PubMed ID: 34156.
    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 molecular oxygen to form superoxide. The overall Km range for this electron transfer is 0.4 to 42.1 X 10(-4) M. We postulate that the formation of the "site-specific free radical/ intermediate is central to the cytotoxic action of these antibiotics.
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