Enhancement of DNA chain breakage by bleomycin A2 in the presence of microsomes and reduced nicotinamide adenine dinucleotide phosphate.
Chain breakage in DNA induced by bleomycin A2 (BLM) was enhanced more than 150-fold by the reduced nicotinamide adenine dinucleotide phosphate-dependent electron transport system of rat liver microsomes. However, the enhancement effect on DNA was partially reduced by the preincubation of BLM with the microsomal systems. BLM-Cu2+ was found to stimulate considerably microsomal reduced nicotinamide adenine dinucleotide phosphate-dependent oxygen consumption and malondialdehyde formation, whereas BLM inhibited both of the effects. These findings suggest that the pharmacological action of BLM is strongly affected by a membrane system, such as microsomes, that produces free radicals.
D000818:Animals; D001761:Bleomycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002614:Chelating Agents; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004579:Electron Transport / Q000187:drug effects; D005609:Free Radicals; D066298:In Vitro Techniques; D008315:Malondialdehyde / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats
D002614:Chelating Agents; D005609:Free Radicals; D001761:Bleomycin; D008315:Malondialdehyde; D009249:NADP; D003300:Copper; D004247:DNA