ToxSci Advance Access published online on January 29, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp018
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Influence of dietary co-exposure 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 nyagode01@yahoo.com mojames{at}ufl.edu
Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, Louisiana kkleinow{at}vetmed.lsu.edu
Corresponding author: Margaret O. James, Department of Medicinal Chemistry, 1600 SW Archer Road, University of Florida, Gainesville FL 32610-0485, mojames{at}ufl.edu, Phone: 352 273 7707 Fax: 352 846 1972
Received November 11, 2008; revision received December 23, 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, OH-MXC and 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 six days with 2 mg/kg 14C-MXC alone or 2 mg/kg 14C-MXC and 2 mg/kg benzo(a)pyrene. On day seven, blood and tissue samples were taken for analysis. Hepatic ethoxyresorufin O-deethylase activity was 10-fold higher in the benzo(a)pyrene-treated catfish, indicating CYP1A induction. More MXC-derived radioactivity remained in control (42.8 ± 4.1%) than benzo(a)pyrene-induced catfish (28.5 ± 3.2%), mean percent total dose ± S.E. 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 co-exposed to benzo(a)pyrene 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.