title: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Ngui
authors.forename: S M
authors.initials: SM
authors.lastname: Bandiera
mesh_terms: D000818:Animals; D001140:Aroclors / Q000633:toxicity*; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction; D015151:Immunoblotting; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
chemical_list: D001140:Aroclors; D015415:Biomarkers; D004785:Environmental Pollutants; C026987:aroclor 1260; D003577:Cytochrome P-450 Enzyme System