US EPA

2173616 

Journal Article 

Differences in the induction of carboxylesterase isozymes in rat liver microsomes by xenobiotics 

Hosokawa, M; Maki, T; Satoh, T 

1988 

Yes 

Biochemical Pharmacology
ISSN: 0006-2952
EISSN: 1873-2968 

NIOSH/00181853 

37 

13 

2708-2711 

English 

3390232 

The induction of carboxylesterase (CE) isozymes in hepatic microsomes by xenobiotics was studied in rats. Sprague-Dawley-rats were injected intraperitoneally with 150mg/kg trans-stilbene-oxide (1439072) (TSO) daily five times or 40mg/kg aroclor-1254 (11097691) daily three times, or orally with 600mg/kg aminopyrine (58151) daily six times or 300mg/kg clofibrate (637070) daily three times. They were killed 24 hours after the last dose and the livers were removed. The microsomal and cytosol fractions were prepared and assayed for specific CE activity using p-nitrophenylacetate (PNPA), malathion, isocarboxazid, butanilicaine, or acyl-coenzyme-A (acylcoA) as substrates. The CE isozymes RL1, RH1, and RH2 were determined by an immunochemical technique. Aminopyrine significantly induced CE activity toward isocarboxazid, malathion, and PNPA. RL1 was increased by aminopyrine more in females and RL2 more in male rats. TSO and aroclor-1254 increased the amount of the RL2 isozyme, which paralleled the increase in CE activity toward isocarboxazid. Clofibrate significantly increased microsomal CE activity toward PNPA, butanilicaine, isocarboxazide, and acylcoA. Specific CE activity toward acylcoA was also induced in the cytosol fraction. All three CE isozymes were induced by clofibrate in the microsomes but not in the cytosol. The authors conclude that aminopyrine, TSO, aroclor-1254, and clofibrate induce CE RL1, RH2, and RL2 isozymes to different extents.