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ToxSci Advance Access originally published online on July 25, 2003
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Toxicological Sciences 75, 249-259 (2003)
Copyright © 2003 by the Society of Toxicology

BIOTRANSFORMATION AND TOXICOKINETICS

Dieldrin Stimulates Biliary Excretion of 14C-Benzo[a]pyrene Polar Metabolites but Does Not Change the Biliary Metabolite Profile in Rainbow Trout (Oncorhyncus mykiss)

Melanie L. Barnhill, Marie V. M. Rosemond and Lawrence R. Curtis1

Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331

Activities of hepatic microsomal and cytosolic epoxide hydrolases, accumulation of dieldrin in liver, and in vivo metabolism and disposition of the polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BP), were examined in rainbow trout pretreated with dieldrin, a chlorinated cyclodiene insecticide. Rainbow trout were fed 0.3 mg dieldrin/kg/day for 9 weeks and the same dose of dieldrin for 9 weeks, followed by 3 weeks on control diet (12 weeks). Fish then received an intraperitoneal (ip) challenge dose of 14C-BP (10 µmol/kg). Dieldrin pretreatment significantly elevated the concentration of 14C-BP in bile (142% and 200% at 9 and 12 weeks, respectively), but not liver or fat. Extraction of bile subsamples confirmed dieldrin pretreatment significantly stimulated total biliary excretion of14C-BP polar metabolites (244% and 221% at week 9 and 12, respectively). The complex metabolism of BP characterized the in vivo state of the CYP system, UDP-glucuronyltransferases, and sulfotransferases. Bile was extracted and then hydrolyzed by ß-glucuronidase and arylsulfatase to regenerate BP metabolites conjugated by phase II enzymes. Evaluation of biliary polar metabolite profiles of 14C-BP revealed no significant differences between control and dieldrin-fed fish. There was no selective enhancement of any particular metabolite, or formation of a novel metabolite with dieldrin pretreatment. This research confirmed that enhanced biliary excretion, following chronic dieldrin exposure, was not explained by induction of xenobiotic metabolizing enzymes. The results are consistent with induction of hepatic intracellular trafficking proteins in dieldrin-fed fish.

Key Words: benzo[a]pyrene; biliary excretion; dieldrin; in vivo metabolism; rainbow trout.


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