Comparison of in vivo and in vitro methods for assessing the effects of carbon tetrachloride on the hepatic drug-metabolizing enzyme system.
The effect of a single i.p. injection of 0, 20, 200, and 1000 microliter/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 this 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 glucuronyltransferase 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.
Chadwick
R W
RW
Environmental Research Center, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Copeland
M F
MF
Carlson
G P
GP
Trela
B A
BA
Most
B M
BM
D000438:Alcohols / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity*; D002733:Chlorophenols / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005036:Ethylmorphine / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors; D001556:Hexachlorocyclohexane / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013466:Sulfurtransferases / Q000037:antagonists & inhibitors
D000438:Alcohols; D002733:Chlorophenols; D001556:Hexachlorocyclohexane; D002251:Carbon Tetrachloride; D014453:Glucuronosyltransferase; D013466:Sulfurtransferases; D005036:Ethylmorphine