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Molecular Pharmacology, Vol 13, 901-910, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics
1 Laboratory of Clinical Biochemistry, Baltimore Cancer Research Center, National Cancer Institute,
Baltimore, Maryland 21211
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, 
-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.
Note:
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.
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