Studies on the interaction of bleomycin A2 with rat lung microsomes. III. Effect of exogenous iron on bleomycin-mediated DNA chain breakage.
The interaction of bleomycin A2 with rat lung microsomes results in bleomycin-mediated DNA chain breakage due to the mixed-function oxidase catalyzed activation of bleomycin. This study demonstrates that the addition of exogenous Fe3+ significantly enhances the bleomycin-mediated cleavage of DNA deoxyribose, that the enhancing effect of Fe3+ is maximum when a 1:1 ratio of bleomycin to Fe3+ is achieved and that either NADPH or NADH can serve as pyridine cofactors for this reaction. Since the activation of bleomycin can be facilitated by iron in the Fe2+ form, these observations support the hypothesis that the mixed-function oxidase system may serve to maintain either adventitious or exogenous iron in the Fe2+ form. In the absence of DNA, the interaction of bleomycin with rat lung microsomes results in the self-inactivation of bleomycin, a reaction which is also enhanced by the addition of exogenous Fe3+. Thus, the microsomal mixed-function oxidase system represents an efficient biological system for the 'activation-inactivation' of bleomycin.
D000818:Animals; D001761:Bleomycin / Q000378:metabolism* / Q000494:pharmacology; D003300:Copper / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005290:Ferric Compounds / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology
D005290:Ferric Compounds; D001761:Bleomycin; D003300:Copper; D004247:DNA; D007501:Iron; D006899:Mixed Function Oxygenases; D013482:Superoxide Dismutase