Biotransformation of methoxychlor and selected xenobiotics in channel catfish (Ictalurus punctatus) and largemouth bass (Micropterus salmoides)

The demethylation of methoxychlor (MXC), an organochlorine pesticide, gives rise to the mono- and bis-demethylated primary metabolites OHMXC and HPTE respectively which are estrogenic and antiandrogenic. In vitro results show that the efficiency of their sulfation is some times as much as ten times lower than their glucuronidation efficiency, both in the liver and intestine. The combined rates of the formation of the glucuronide and sulfate conjugation of OHMXC and HPTE are much lower than those of the cytochrome P450-dependent rates of their formation. This might mean that the expected detoxification pathways are inefficient at aiding the elimination of these potentially harmful metabolites after environmental exposure of the channel catfish to MXC. Sulfotransferases have generally been considered to be non-inducible in fish. We report increased sulfation, especially of 3-hydroxybenzo-[a]-pyrene, by 3-methylcholanthrene (3MC)-treated channel catfish when compared to control fish. Efficiency of hepatic sulfation increased from 930 +/- 366muL/min/mg (mean +/- SE) in control to 2976 +/- 385 in 3MC-treated fish, while that of intestinal sulfation also went from 4301 +/- 1160 to 8602 +/- 230.;In an in vivo study, the co-exposure of catfish to benzo-[a]-pyrene and radiolabeled MXC resulted in enhanced elimination of MXC. In control samples, 45.4 +/- 8.9% (mean +/- SE) of radioactivity was recovered as compared to 30.2 +/- 6.8% in benzo-[a]-pyrene-induced catfish. Of the dose recovered in the tissues analyzed, nearly 90% was found in bile, muscle and fat deposits. Analysis showed that OHMXC, HPTE and their glucuronide conjugates were formed, but no sulfate conjugates were detected. Potentially toxic metabolites of MXC were present in the edible muscle tissue.;Probe substrates that yield highly fluorescent metabolites in isozyme-specific P450 reactions are popular because of their convenience compared to other substrates. We report that in the channel catfish and largemouth bass, the 7-benzyloxy-4-(trifluoromethyl)-coumarin O-debenzylase (BFCOD) assay, used successfully in several mammalian systems, does not correlate well with 6beta-hydroxylation of testosterone, the standard marker for CYP3A. The BFCOD assay may therefore not be an indicator of CYP3A activity in these two species.