Toxicological Sciences, Vol 47, 52-61, Copyright © 1999 by Society of Toxicology
PJ Korytko, AC Casey, B Bush and FW Quimby
Induction of cytochrome P450 isoforms, specifically CYP1A1, and their
catalytic activities are potential biomarkers of environmental
contamination by polychlorinated biphenyls (PCBs). In this study, dogs were
exposed to 25 ppm or 5 ppm Aroclor 1248 (PCB mixture) daily in their diet
for 10 or 20 weeks, respectively. Relative to controls, hepatic microsomes
from dogs dosed with PCBs had higher levels of CYP1A1 detected in
immunoblots and higher levels of EROD activity, but low levels of induction
for CYP2B and PROD activity. Concentrations of 96 PCB congeners in serum
and liver were evaluated using capillary chromatography. Results showed
that all dogs exposed to PCB mixtures had higher levels of PCB in serum and
liver. Dogs preferentially sequestered highly chlorinated PCB congeners in
liver relative to serum. With these experiments, we demonstrated that EROD
activity was a potentially sensitive marker of PCB exposure at 5 and 25
ppm. Furthermore, CYP1A1 and EROD activity were maximally induced in dogs
consuming dietary concentrations only 2.5 times the maximal permissible
level for human food (FDA). The value of CYP1A1 induction as a biomarker of
PCB exposure was tenuous because neither CYP1A1 levels nor EROD activity
correlated with total PCB body burden. However, a small subset of congeners
were identified in liver that may strongly influence EROD and PROD
induction. Finally, two dogs in the 25 ppm dose group were fasted for 48 h.
After 24 h of fasting, several new congeners appeared in the serum and
remained in the serum for the remainder of the fast. The fast caused a 293%
increase in PCB concentration in serum. This increase has strong
implications regarding mobilization of toxic PCBs in wildlife during
fasting (e.g., migration, hibernation).
ARTICLES
Induction of hepatic cytochromes P450 in dogs exposed to a chronic low dose of polychlorinated biphenyls
Field of Environmental Toxicology, Center for the Environment, Cornell University, Ithaca, NY 14853, USA.
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