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J.Health Sci., 49(3), 229-232, 2003
Methoxychlor Induces CYP2C11 to Convert Itself into Hormonally Active Metabolites
Eriko Mikamo, Shingo Harada, Jun-ichi Nishikawa, and Tsutomu Nishihara*
Laboratory of Environmental Biochemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan
Methoxychlor (MXC), a chlorinated hydrocarbon pesticide, adversely affects the hormonal system in animals by producing metabolites with estrogenic activity. When methoxychlor was administrated to male rats for 7 days, CYP2C11 as well as its 2B1/2 and 3A1 was induced in the liver. In addition, an in vitro study using recombinant CYPs and HPLC analysis showed that only the CYP2C11 subfamily converted MXC into hormonally active metabolites, such as demethylated derivatives, not 2B1 and 3A1. These findings suggest that MXC accelerates the conversion of itself into hormonally active metabolites, leading to disruption of the endocrine system.
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