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.