Induction of hepatic CYP2B is a more sensitive indicator of exposure to aroclor 1260 than CYP1A in male rats.
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.
Ngui
J S
JS
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Bandiera
S M
SM
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
D001140:Aroclors; D015415:Biomarkers; D004785:Environmental Pollutants; C026987:aroclor 1260; D003577:Cytochrome P-450 Enzyme System