title: NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals.
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.
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003579:Cytochrome Reductases / Q000378:metabolism*; D004579:Electron Transport; D005609:Free Radicals; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010101:Oxygen Consumption; D011809:Quinones / Q000378:metabolism; D051381:Rats
chemical_list: D000903:Antibiotics, Antineoplastic; D005609:Free Radicals; D011809:Quinones; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D003579:Cytochrome Reductases; D009251:NADPH-Ferrihemoprotein Reductase