Degradation of DNA by metalloanthracyclines: requirement for metal ions.
Metallodaunomycin has been shown to cleave DNA only in the presence of oxygen, a reducing agent and a metal ion under reaction conditions similar to those used for the cuprous-phenanthroline complex. The intermediacy of 02-. and H2O2 has been substantiated by experiments with superoxide dismutase and catalase, respectively. Only partial inhibition by OH. scavengers was observed. An important feature of the reaction is that no specificity for Cu(II) was observed. This observation has led us to propose a reaction mechanism different from that proposed for the cuprous-phenanthroline complex. The mechanism proposed includes a catalytic role for metal ions other than Cu(II) as well as the direct participation of products of metal-catalyzed redox reactions such as semiquinone and/or hydroquinone of daunomycin.
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D001565:Benzoates / Q000494:pharmacology; D019817:Benzoic Acid; D002374:Catalase / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003300:Copper / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D003630:Daunorubicin / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D008623:Mercaptoethanol / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D011067:Poly dA-dT / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000085:Acetates; D001565:Benzoates; D006878:Hydroxides; D011067:Poly dA-dT; D017665:Hydroxyl Radical; D008623:Mercaptoethanol; D003300:Copper; D019817:Benzoic Acid; D004247:DNA; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D019342:Acetic Acid; D010100:Oxygen; D003630:Daunorubicin