Cytochrome P-450-dependent fragmentation of DNA in reconstituted membranes.
Membrane vesicles containing various forms of rabbit liver microsomal cytochromes P-450 and NADPH-cytochrome P-450 reductase were found to degrade plasmid DNA in an NADPH-requiring reaction. When cytochrome P-450 was replaced by cytochrome b5, only a negligible extent of DNA disintegration occurred. The complete inhibition of the process by hydroxyl radical scavengers, superoxide dismutase and catalase, indicated an iron-catalyzed Haber-Weiss reaction for the generation of hydroxyl radicals that subsequently react with the nucleic acid.
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010957:Plasmids; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000494:pharmacology
D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D002374:Catalase; D013482:Superoxide Dismutase; D009251:NADPH-Ferrihemoprotein Reductase; D013890:Thiourea; D004121:Dimethyl Sulfoxide