Abstract
Adriamycin, daunorubicin, and other anthracycline antibiotics dramatically augment electron flow from NADPH to molecular oxygen in rat liver microsomes and heart sarcosomes. This process is enzymatic, is dependent on NADPH (Km = 420 µM), has a pH optimum of 8.0-8.5, and is inducible by phenobarbital. The Km values for the anthracycline antibiotics range from 100 to 400 µM. Although SKF 525-A and carbon monoxide do not inhibit the anthracycline stimulation, α-tocopherol and p-hydroxymercuriphenylsulfonic acid inhibit both anthracycline-augmented and endogenous oxygen consumption. Electron spin resonance studies show that the anthraquinone nucleus of the anthracycline is reversibly converted to a free radical semiquinone, which serves to shuttle electrons to oxygen. This enhanced free radical formation may function as the toxic and/or active principle of anthracycline chemotherapy.
ACKNOWLEDGMENTS We appreciate the help of Dr. Hideo Kon, Laboratory of Chemical Physics, National Institute of Arthritis, Metabolic, and Digestive Diseases, in obtaining the ESR spectra, and the efforts of Mrs. Barbara Dressel in the preparation of the manuscript.
- Copyright © 1977 by Academic Press, Inc.
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