Metabolism of methoxychlor by Cunninghamella elegans ATCC36112.
Methoxychlor is considered as pro-estrogen, while some of its metabolites are more potent endocrine disruptors than the parent insecticide. Major activation of methoxychlor is through cytochrome P450-catalyzed demethylation to bisphenol A-like metabolites. Cunninghamella elegans is a well-known fungal species with its strong resemblance of the xenobiotic metabolism of the mammalian system. In this study, the metabolism of methoxychlor was investigated with the corresponding organism. Methoxychlor was rapidly transformed to approximately 11 metabolites in phase I metabolism, including oxidation, hydroxylation, and dechlorination. Concentrations of phase I metabolites reached a maximum at 4-6 days and gradually decreased until the end of the experiments. Most metabolites from the phase I reaction were further transformed to sugar conjugates. Approximately 11 or more glucose conjugates were found in culture supernatants and gradually increased, while no glucuronides were observed throughout the experiments. Piperonyl butoxide and chlorpyrifos strongly inhibit the degradation of methoxychlor and concomitant accumulation of metabolites, indicating cytochrome P450 mediated metabolism. Little or no glycosides were detected in chlorpyrifos- and piperonyl butoxide-treated cultures. From the results, Cunninghamella elegans has shown strong similarities of the phase I metabolism of methoxychlor, while the conjugation reaction is different from those of animal metabolism.
Keum
Young Soo
YS
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea.
Lee
Youn Hyung
YH
Kim
Jeong-Han
JH
D020093:Cunninghamella / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007306:Insecticides / Q000378:metabolism*; D007700:Kinetics; D008731:Methoxychlor / Q000378:metabolism*
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007306:Insecticides; D003577:Cytochrome P-450 Enzyme System; D005947:Glucose; D008731:Methoxychlor