Chloroethylaziridine-Induced Xenobiotic Metabolism Gene Expression in the Mouse Lung

Date
2014-04-15
Authors
Dickson, Mackenzie
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Altmetrics
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Animal Science
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Animal Science
Abstract

While chemotherapy is championed as the primary treatment for cancer patients around the world, there are adverse side effects including infertility. Specifically, the drug phosphoramide mustard (PM), a chemotherapy metabolite, was researched in this study. PM is recognized as the most genotoxic metabolite of a widely used chemotherapy drug, cyclophosphamide, and is an alkylating agent that interferes with DNA replication and depletes all ovarian follicle types, leading to infertility. PM can be metabolized to chloroethylaziridine (CEZ), a volatile compound previously reported to expire from rat lungs. Using 14-week-old lean and obese mice, levels of metabolism gene expression following intraperitoneal PM exposure were analyzed. Three days after exposure, lungs were collected, RNA extracted, and real-time PCR performed. Microsomal epoxide hydrolase (mEH), a key metabolizing enzyme, was increased (P< 0.05, 5.4-fold) with obesity, compared to the lean controls. PM-treated obese mice had increased (P< 0.05, 1.5-fold) mEH levels compared to obese, vehicle control treated mice. The results of this study could have significant implications, like compromised lung capacity or fertility, for patients or the nurses and doctors who are administering the drug, thus being exposed to CEZ as the patients metabolize the chemotherapy and expire CEZ into the air.

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