IMMUNOQUANTITATION AND MICROSOMAL MONOOXYGENASE ACTIVITIES OF HEPATICCYTOCHROMES P4501A AND P4502B AND CHLORINATED-HYDROCARBON CONTAMINANTLEVELS IN POLAR BEAR (URSUS-MARITIMUS)

Contamination of the Arctic ecosystem by anthropogenic compounds has r esulted in exposure of polar bear (Ursus maritimus) to lipophilic chlo rinated hydrocarbon contaminants (CHCs) accumulated through the marine food web, Liver samples were collected from 16 adult male polar bears in the Canadian arctic and subjected to chemical analysis for CHCs an d metabolites, determination of alkoxyresorufin O-dealkylase activitie s, and immunoquantitation of cytochrome P450 (CYP) protein levels, We report on the relationships between the hepatic microsomal levels of i mmunoreactive CYP1A and CYP2B isozymes, catalytic activities, and hepa tic CHC and metabolite concentrations in polar bear, We specifically e xplored the influence of several CHCs on the induction of hepatic CYP in polar bear and the potential use of immunoassay quantitation as a b ioindicator of CHC exposure, Polychlorinated biphenyls (PCBs) classed as CYP1A and mixed CYP1A/CYP2B inducers accounted for about 25% of the total PCB residues present (18,680 +/- 5053 ng/g lipid), CYP1A protei n content correlated strongly with hepatic levels of PCBs, PCDDs (0.03 2 +/- 0.018 ng/g lipid), and PCDFs (0.011 +/- 0.007 ng/g lipid) and th eir corresponding toxic equivalents (TEQ, 0.377 +/- 0.182 ng/g lipid). Mono-ortho-CB-156, CB-157, and CB-105 were the predominant TEQ contri butors, Correlations between CYP2B protein content and CHC residue lev els in polar bear liver suggested that ortho-chlorine-substituted PCBs and chlordanes were the major contributors to CYP2B induction, CYP1A and CYP2B contents were therefore good indicators of CHC exposure in p olar bear liver, Ethoxyresorufin, pentoxyresorufin, and benzyloxyresor ufin O-dealkylase activities increased with increasing CYP1A protein c ontent up to protein levels of approximately 5 pmol/mg, suggesting tha t all three activities were primarily CYP1A-mediated, These results we re substantiated by antibody inhibition experiments, In summary, immun oquantitated CYP1A and CYP2B isozymes are a more reliable measure of e xposure to CHC inducers than alkoxyresorufin O-dealkylase activities i n polar bear. (C) 1996 Academic Press, Inc.