Abstract
The anticancer drug bleomycin forms a complex with metal ions, e.g. iron ions. Only the reduced complex is able to bind molecular oxygen1. This “activated bleomycin”2 induces DNA strand breaks and malondialdehyde (MDA) formation which originates from the oxidative cleavage of deoxyribose (Fig. 1). “Activated bleomycin” may be formed by low molecular reducing agents1, but also by enzymatic reduction of bleomycin-Fe(III)3,4. We wondered whether NADPH- cytochrome P-450 reductase and NADH-cytochrome b5 reductase are involved in this reduction step. Furthermore, we were interested whether these reductases present in intact cell nuclei are able to catalyze the reduction of bleomycin-Fe(III), the formation of active oxygen and the oxidative cleavage of nuclear DNA. This is important, because DNA damage catalyzed by nuclear reductases may be directly related to cell toxicity induced by bleomycin.
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Kappus, H., Mahmutoglu, I. (1990). Reduction of Bleomycin-Fe by Reductases and Active Oxygen Formation. In: Adams, G.E., Breccia, A., Fielden, E.M., Wardman, P. (eds) Selective Activation of Drugs by Redox Processes. NATO ASI Series, vol 198. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3768-7_7
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DOI: https://doi.org/10.1007/978-1-4615-3768-7_7
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