title: Comparative hepatic activity of xenobiotic-metabolizing enzymes and concentrations of organohalogens and their hydroxylated analogues in captive Greenland sledge dogs (Canis familiaris).
abstract: A captive study was performed with Greenland sledge dogs (Canis familiaris) fed a naturally organohalogen-contaminated diet (Greenland minke whale [Balaenoptera acutorostrata] blubber; exposed group) or a control diet (pork fat; control group). The catalytic activity of major xenobiotic-metabolizing phase I and II hepatic microsomal enzymes was assessed. Relative to control dogs, ethoxyresorufin-O-deethylase (EROD) activity in exposed dogs was twofold higher (p = 0.001). Testosterone hydroxylation yielded 6beta- and 16beta-hydroxy (OH) testosterone and androstenedione, with higher rates of production (23-27%; p < or = 0.03) in the exposed individuals. In the exposed dogs, epoxide hydrolase (EH) activity was 31% higher (p = 0.02) relative to the control dogs, whereas uridine diphosphoglucuronosyl transferase (UDPGT) activity was not different (p = 0.62). When the exposed and control dogs were combined, the summed (sigma) plasma concentrations of OH-polychlorinated biphenyl (PCB) congeners were predicted by plasma sigmaPCB concentrations and EROD activity (p < or = 0.04), whereas testosterone hydroxylase, EH, and UDPGT activities were not significant predictors of these concentrations. Consistent results were found for individual OH-PCB congeners and their theoretical precursor PCBs (e.g., 4-OH-CB-187 and CB-183, and 4-OH-CB-146 and CB-146) and for EROD activity. No association was found between sigmaOH-polybrominated diphenyl ether (PBDE) and sigmaPBDE plasma concentrations, or between potential precursor-metabolite pairs, and the enzyme activities. The present results suggest that liver microsomal EROD activity and plasma PCB concentrations have a greater (e.g., relative to EH activity) predictive power for the occurrence of plasma OH-PCB residues in sledge dogs. These results also suggest that plasma OH-PBDEs likely are not products of cytochrome P450-mediated transformation but, rather, are accumulated via the diet.
authors.affiliation: Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario K1A 0H3.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Verreault
authors.forename: France
authors.initials: F
authors.lastname: Maisonneuve
authors.forename: Rune
authors.initials: R
authors.lastname: Dietz
authors.forename: Christian
authors.initials: C
authors.lastname: Sonne
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Letcher
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004285:Dogs; D004851:Epoxide Hydrolases / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D006116:Greenland; D006219:Halogens / Q000378:metabolism*; D006900:Hydroxylation; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009930:Organic Chemicals / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D006219:Halogens; D009930:Organic Chemicals; D015262:Xenobiotics; D006899:Mixed Function Oxygenases; D019363:Cytochrome P-450 CYP1A1; D014453:Glucuronosyltransferase; D004851:Epoxide Hydrolases