Nuclear catalyzed antibiotic free radical formation.

Abstract

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.