Redox transformations of quinone antitumor drugs in liver microsomes.
The hydroxyl radical has been spin trapped in microsomal and purified NADPH-cytochrome P-450 reductase systems in the presence of adriamycin, daunomycin and mitomycin C. The presence of a lag period in quinone-stimulated spin-adduct formation is associated with oxygen removal upon its reduction to H2O2. The hydroxy radical generation has been stimulated by the Fe-EDTA complex and completely inhibited by catalase. The mechanism of redox transformations of anthracyclines in a microsomal system has been proposed The single electron reduced quinone-containing anticancer antibiotics play the following roles: (i) they reduce oxygen to H2O2 and (ii) they reduce the ferric ions necessary for H2O2 decomposition with hydroxyl radical formation.
Rumyantseva
G V
GV
Institute of Chemical Kinetics and Combustion, Novosibirsk, USSR.
Weiner
L M
LM
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001711:Biotransformation; D004578:Electron Spin Resonance Spectroscopy; D006878:Hydroxides; D017665:Hydroxyl Radical; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D009279:Naphthacenes / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000903:Antibiotics, Antineoplastic; D006878:Hydroxides; D009279:Naphthacenes; D017665:Hydroxyl Radical; D009251:NADPH-Ferrihemoprotein Reductase