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COMPARISON OF IN VIVO AND IN VITRO METHODS FOR ASSESSING THE EFFECTS OF REPEATED DOSING WITH CARBON TETRACHLORIDE ON THE HEPATIC DRUG-METABOLIZING ENZYME SYSTEM (JOURNAL VERSION)
Citation:
Chadwick, R., M. Copeland, G. Carlson, B. Trela, AND B. Most. COMPARISON OF IN VIVO AND IN VITRO METHODS FOR ASSESSING THE EFFECTS OF REPEATED DOSING WITH CARBON TETRACHLORIDE ON THE HEPATIC DRUG-METABOLIZING ENZYME SYSTEM (JOURNAL VERSION). U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-88/264 (NTIS PB89143705), 1988.
Description:
The effect of a single i.p. injection of 0, 20, 200, and 1000 microliters/kg carbon tetrachloride on the activity of the hepatic drug-metabolizing enzyme system was measured in the rat by a model substrate assay, employing lindane (gamma-hexachlorocyclohexane), and by a battery of in vitro enzyme assays. The data in the study indicated that carbon tetrachloride had a biphasic influence on the phase I reactions with the lowest dose inducing a significant increase in enzyme activity while the highest dose produced significant inhibition. Significant CCl4-induced reductions in glucaronyltransferase and sulfotransferase activities were also observed while the effect on glutathione-S-transferase was ambiguous. The in vivo and in vitro assays showed good agreement. (Copyright (c) 1988 Elsevier Science Publishers B.V.)