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Induction of hepatic CYP2B is a more sensitive indicator of exposure to aroclor 1260 than CYP1A in male rats.

Abstract：

:To evaluate the effect of exposure to an environmentally relevant polychlorinated biphenyl mixture, adult male rats were treated with Aroclor 1260 for 7 days and levels of several cytochrome P450 (CYP) enzymes were measured in liver microsomes prepared 3 days after the last dose. Treatment with Aroclor 1260 at dosages ranging from 0.5 to 50 mg/kg/day had no effect on body weight, but liver weight was increased significantly in rats treated with the two highest dosages. Of the monooxygenase activities examined, benzyloxyresorufin O-dealkylase and testosterone 16beta-hydroxylase activities were increased to the greatest extent with maximal induction of both activities reached at 5 mg/kg/day. Densitometric quantitation of blots probed with antibody against CYP2B revealed that CYP2B1 and CYP2B2 protein levels were increased approximately 55-fold and 16-fold, respectively, after treatment with Aroclor 1260 at 5 mg/kg/day. Ethoxyresorufin O-deethylase activity and CYP1A1 protein levels displayed linear dose-dependent increases, but the hepatic CYP1A1 content did not exceed 10% that of CYP2B1 at all dosages of Aroclor 1260. Microsomal CYP3A- and CYP2A1-mediated enzyme activities and protein levels were also increased by treatment with Aroclor 1260 but to a lesser extent, whereas CYP2C11-mediated enzyme activities and protein levels were reduced. A separate time-course study showed that induction of CYP2B, but not of CYP1A, enzymes persisted for at least 48 days after treatment with Aroclor 1260 at 10 mg/kg/day. In summary, the results indicate that induction of CYP2B enzymes is a more sensitive biomarker of exposure to Aroclor 1260 than CYP1A.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Ngui JS,Bandiera SM

doi

10.1006/taap.1999.8787

subject

Has Abstract

pub_date

1999-12-01 00:00:00

pages

160-70

issue

2

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(99)98787-2

journal_volume

161

pub_type

杂志文章

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