Involvement of cytochrome P450 2F2 in bioactivation of 1,1-dichloroethylene in mouse lung

Involvement of cytochrome P450 2F2 in bioactivation of 1,1-dichloroethylene in mouse lung

1,1-Dichloroethylene (DCE) elicits pneumotoxicity upon exposure. This toxicity is mediated by CYP2E1-dependent metabolism of DCE to an epoxide, which conjugates with glutathione (GSH) to form 2-S-glutathionyl acetate (conjugate [C]). In addition to CYP2E1, available data suggest that other P450 enzy...

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Main Author: Simmonds, Andrea C
Format: Dissertation
Language:English
Published: ProQuest Dissertations & Theses 01-01-2003
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Toxicology
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Abstract 1,1-Dichloroethylene (DCE) elicits pneumotoxicity upon exposure. This toxicity is mediated by CYP2E1-dependent metabolism of DCE to an epoxide, which conjugates with glutathione (GSH) to form 2-S-glutathionyl acetate (conjugate [C]). In addition to CYP2E1, available data suggest that other P450 enzymes might be involved in DCE metabolism to the epoxide. We hypothesized that CYP2F2 (mouse) is an additional P450 that metabolizes DCE. To test this hypothesis, in vitro and in vivo studies were performed using liquid chromatography/mass spectrometry (LC/MS) and Western blot as well as morphologic analyses. Formation of conjugate [C] was determined by LC/MS analysis of microsomal incubations with DCE and lung cytosolic fractions isolated after DCE treatment. (Abstract shortened by UMI.)
AbstractList 1,1-Dichloroethylene (DCE) elicits pneumotoxicity upon exposure. This toxicity is mediated by CYP2E1-dependent metabolism of DCE to an epoxide, which conjugates with glutathione (GSH) to form 2-S-glutathionyl acetate (conjugate [C]). In addition to CYP2E1, available data suggest that other P450 enzymes might be involved in DCE metabolism to the epoxide. We hypothesized that CYP2F2 (mouse) is an additional P450 that metabolizes DCE. To test this hypothesis, in vitro and in vivo studies were performed using liquid chromatography/mass spectrometry (LC/MS) and Western blot as well as morphologic analyses. Formation of conjugate [C] was determined by LC/MS analysis of microsomal incubations with DCE and lung cytosolic fractions isolated after DCE treatment. (Abstract shortened by UMI.)
Author Simmonds, Andrea C
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Snippet 1,1-Dichloroethylene (DCE) elicits pneumotoxicity upon exposure. This toxicity is mediated by CYP2E1-dependent metabolism of DCE to an epoxide, which...
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Title Involvement of cytochrome P450 2F2 in bioactivation of 1,1-dichloroethylene in mouse lung
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