THE PH-DEPENDENT REDUCTION OF ADRIAMYCIN CATALYZED BY NADH-CYTOCHROMEB(5) REDUCTASE

Adriamycin is a redox active antineoplastic antibiotic that upon reduc tion can, in the presence of oxygen, redox cycle to form reactive oxyg en species, while in anaerobiosis can generate a reactive quinone meth ide. NADH:cytochrome b(5) reductase catalysed the reduction of adriamy cin at pH 6.6 with an apparent K-m of 1.8 mu M; at pH 7.6, no measurab le reduction of adriamycin occurred. Aerobically, in the presence of e nzyme and NADH, adriamycin stimulated oxygen consumption and concomita nt accumulation of hydrogen peroxide. At pH 7.6, no discernible oxygen consumption nor detectable hydrogen peroxide generation was observed. The findings demonstrate that NADH:cytochrome b(5) reductase is capab le of reducing adriamycin, in a pH-dependent manner, to species that c an redox cycle in the presence of oxygen to form reactive oxygen molec ules and thus may contribute to the generation of oxidative stress, a phenomenon suggested to be involved in both the toxicity and the antin eoplastic activity of adriamycin.