ToxSci Advance Access originally published online on January 29, 2009
Toxicological Sciences 2009 108(2):320-329; doi:10.1093/toxsci/kfp018
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Influence of Dietary Coexposure to Benzo(a)pyrene on the Biotransformation and Distribution of 14C-Methoxychlor in the Channel Catfish (Ictalurus punctatus)
* Department of Medicinal Chemistry, University of Florida, Gainesville, Florida
Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, Louisiana
1 To whom correspondence should be addressed at Department of Medicinal Chemistry, 1600 SW Archer Road, University of Florida, Gainesville, FL 32610-0485. Fax: (352) 846-1972. E-mail: mojames{at}ufl.edu.
Received November 11, 2008; accepted January 22, 2009
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Abstract |
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Methoxychlor (MXC) is an organochlorine pesticide whose mono- and bis-demethylated metabolites, 2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)-1,1,1-trichloroethane (OH-MXC) and 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), respectively, are estrogenic and antiandrogenic. Studies in vitro showed that treatment of channel catfish with a polycyclic aromatic hydrocarbon increased phase I and phase II metabolism of MXC. To determine the in vivo significance, groups of four channel catfish were treated by gavage for 6 days with 2 mg/kg 14C-MXC alone or 2 mg/kg 14C-MXC and 2 mg/kg benzo(a)pyrene (BaP). On day 7, blood and tissue samples were taken for analysis. Hepatic ethoxyresorufin O-deethylase activity was 10-fold higher in the BaP-treated catfish, indicating CYP1A induction. More MXC-derived radioactivity remained in control (42.8 ± 4.1%) than BaP-induced catfish (28.5 ± 3.2%), mean percent total dose ± SE. Bile, muscle and fat contained approximately 90% of the radioactivity remaining in control and induced catfish. Extraction and chromatographic analysis showed that liver contained MXC, OH-MXC, HPTE, and glucuronide but not sulfate conjugates of OH-MXC and HPTE. Liver mitochondria contained more MXC, OH-MXC, and HPTE than other subcellular fractions. Bile contained glucuronides of OH-MXC and HPTE, and hydrolysis of bile gave HPTE and both enantiomers of OH-MXC. The muscle, visceral fat, brain and gonads contained MXC, OH-MXC, and HPTE in varying proportions, but no conjugates. This study showed that catfish coexposed to BaP and MXC retained less MXC and metabolites in tissues than those exposed to MXC alone, suggesting that induction enhanced the elimination of MXC, and further showed that potentially toxic metabolites of MXC were present in the edible tissues.
Key Words: channel catfish methoxychlor residues; in vivo methoxychlor metabolism; induction of methoxychlor metabolism by benzo(a)pyrene.
This work was presented in part at the 14th International symposium on Pollutant Responses in Marine Organisms, Florianopolis, Brazil, May 2007.