Abstract
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 (14)C-MXC alone or 2 mg/kg (14)C-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.