Molecular Pharmacology, Vol 18, 553-558, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Metabolism of Carbon Tetrachloride in Hepatic Microsomes and Reconstituted Monooxygenase Systems and Its Relationship to Lipid Peroxidation

¹ Laboratory of Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
² Department of Physiological Chemistry, University of the Saarland, Homburg (Saar), West Germany
³ Laboratory of Environmental Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

The metabolism of carbon tetrachloride has been investigated in liver microsomes and in reconstituted cytochrome P-450-dependent monoxygenase systems. In both cases cytochrome P-450 appears to be the sole site of carbon tetrachloride reduction. In aerobic incubations of microsomal preparations from phenobarbital-treated rats or rabbits, carbon tetrachloride induces large increases in NADPH oxidation and oxygen uptake. This cofactor utilization is not directly related to monooxygenase-mediated metabolism. Under aerobic conditions carbon tetrachloride induces lipid peroxidation, a reaction which is not inhibited by carbon monoxide. Under anaerobic conditions, carbon monoxide is a potent inhibitor of the cytochrome P-450-mediated reduction of carbon tetrachloride. These facts are inconsistent with a role for carbon tetrachloride metabolism in the potentiation of lipid peroxidation.

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ACKNOWLEDGMENTS We are grateful to Dr. B. Gladen for the statistical evaluation of double reciprocal vs square root functions and to Ms. D. Ritter for preparation of the manuscript.