NUCLEAR CATALYZED ANTIBIOTIC FREE-RADICAL FORMATION

Abstract

Nuclei isolated from rat liver, heart and kidney catalyze O2 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 [anticancer agents]. The Km and Vmax values for NADPH were 2.4 .times. 10-3 M and 3 .times. 10-8 mol O2/min per mg protein and Km values for the antibiotics ranged from 1.4 .times. 10-4 to 5.9 .times. 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 EPR 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.