A pleiotropic response to phenobarbital-type enzyme inducers in the F344/NCr rat. Effects of chemicals of varied structure.

摘要: Abstract The effects of a number phenobarbital-type inducers on selected drug-metabolizing enzymes in male F344/NCr rats were determined by measuring specific catalytic activities and/or the levels RNA which hybridize with probes for corresponding genes. hepatic CYP2B1 assessed CYP2Bl-specific and benzyloxyresorufin O-dealkylase testosterone 16β-hydroxylase activities. Levels CYP3A monitored rate hydroxylation at 6β-position. Microsomal epoxide hydrolase activity was measurement cellular this form assaying hydrolysis benzo[a]pyrene-4,5-oxide. UDP-glucuronyltransferase assayed glucuronidation 3-hydroxybenz[a]anthracene. glutathione S-transferase Ya/Yc measured quantifying total coding proteins. When administered various doses phenobarbital or dichlorodiphenyltrichloroethane (DDT), strong correlations between induction observed. Treatment barbiturates, hydantoins, halogenated pesticides such as DDT α-hexachlorocyclohexane, 2,4, 5,2′,4′,5′-hexachlorobiphenyl, inhibitors clotrimazole clonazepam, structurally-diverse compounds 2-hexanone diallyl sulfide resulted CYP2B1-mediated enzyme certain other forms cytochrome P450, microsomal hydrolase, least one UDP-glucuronyltransferase, multiple S-transferase. This suggests that, class, induce also coordinate pleiotropic response includes these phase I II enzymes.