Spin-trapping and direct electron spin resonance investigations of the redox metabolism of quinone anticancer drugs.
The superoxide free radical has been spin trapped in microsomal incubations containing adriamycin, daunorubicin, and mitomycin C. The time sequence of the appearance of the spin-trapped superoxide and the semiquinone radical metabolite of these quinone-containing anticancer drugs indicates that air oxidation of the semiquinone is responsible for the superoxide formation. Superoxide dismutase prevents the formation of the superoxide spin adducts. Microsomal incubations containing anthracyclines intercalated in DNA produce much less superoxide than incubations free of DNA. The first unambiguous ESR evidence for the semiquinone metabolite of mitomycin C in a biological system is also presented.
D000818:Animals; D004247:DNA / Q000494:pharmacology; D003630:Daunorubicin / Q000378:metabolism*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008937:Mitomycins / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism*; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D008937:Mitomycins; D011809:Quinones; C024703:adriamycin semiquinone radicals; D013481:Superoxides; D004317:Doxorubicin; D004247:DNA; D013482:Superoxide Dismutase; D003630:Daunorubicin