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.
The effect of 7 daily i.p. injections of 0, 2, 20, or 200 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 this study indicated that repeated administration of CCl4 for 7 days significantly increased phase I and phase II reactions in vivo and in vitro. Though there were differences between the responses of the in vivo and in vitro assays, this is the first report of increased hepatic drug-metabolizing enzyme activity from repeated treatment with CCl4.
Chadwick
R W
RW
Health Effects Research Laboratory, 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
D000818:Animals; D002250:Carbon Radioisotopes; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002849:Chromatography, Gas; D005260:Female; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000378:metabolism; D006591:Hexobarbital / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007064:L-Iditol 2-Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344
D002250:Carbon Radioisotopes; D001556:Hexachlorocyclohexane; D006591:Hexobarbital; D002251:Carbon Tetrachloride; D007064:L-Iditol 2-Dehydrogenase; D005952:Glucose-6-Phosphatase