Nuclear catalyzed antibiotic free radical formation.
Nuclei isolated from rat liver, heart, and kidney catalyze oxygen consumption in the presence of reduced pyridine nucleotide (NADPH) and quinone or quinone-imine antibiotics such as Adriamycin, daunorubicin, actinomycin D, mitomycin C, and streptonigrin. The Km and Vmax values for NADPH were 2.4 x 10(-3) M and 3 x 10(-8) mol O2 per min per mg protein and Km values for the antibiotics ranged from 1.4 x 10(-4) M to 5.9 x 10(-6) M. Metabolism of the anthracycline antibiotics, i.e., reductive glycosidase reaction, occurs in reaction mixtures after all oxygen is consumed. During the reaction, free-radical species of Adriamycin and daunorubicin are detectable by electron paramagnetic reasonance spectrometry. These observations indicate that some cytotoxic antibiotics can be activated to a free-radical state at the site where damage to nuclear DNA may result.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004247:DNA / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006358:Hot Temperature; D066298:In Vitro Techniques; D007700:Kinetics; D008854:Microscopy, Electron; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000903:Antibiotics, Antineoplastic; D005609:Free Radicals; D011809:Quinones; D009243:NAD; D009249:NADP; D004247:DNA