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.