Oxy radical formation during redox cycling of the bleomycin-iron (III) complex by NADPH-cytochrome P-450 reductase.

Bleomycin was aerobically incubated with FeCl3, NADPH, isolated rat-liver microsomal cytochrome P-450 reductase and methional. The conversion of methional to ethene, which indicates oxy radicals, was determined. Ethene formation depended on oxygen, NADPH, FeCl3 and the enzyme. About equimolar concentrations of bleomycin and FeCl3 resulted in optimal ethene formation. Dimethyl sulfoxide, mannitol, glycerol, glutathione and glutathione disulfide inhibited ethene formation. These results indicate that oxy radicals are formed after reduction of the bleomycin-Fe-complex by NADPH-cytochrome P-450 reductase.