Recombinant expression of human microsomal epoxide hydrolase protects V79 Chinese hamster cells from styrene oxide- but not from ethylene oxide-induced DNA strand breaks
✍ Scribed by María Elena Herrero; Michael Arand; Jan Georg Hengstler; Franz Oesch
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 281 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
Styrene 7,8-oxide and ethylene oxide are widely range 10 mM to 1 mM styrene 7,8-oxide) measured used genotoxic bulk chemicals, which have been by the alkaline elution technique were significantly associated with potential carcinogenic hazard for lower in the 92hmEH-V79 cells as compared to the occupationally exposed workers. Both epoxides al-mock-transfected cells. The protection against stykylate DNA preferentially at the N-7 position of rene-7,8-oxide genotoxicity in 92hmEH-V79 cells guanine and consequently produce single-strand could be abolished by addition of valpromide, a breaks and alkali labile sites in the DNA of exposed selective inhibitor of microsomal epoxide hydrocells. In order to study the role of human microsomal lase. These results clearly show that the metabolism epoxide hydrolase (hmEH) in protecting cells of styrene 7,8-oxide by hmEH in 92hmEH-V79 cells against genotoxicity of styrene 7,8-oxide and ethyl-was responsible for the protection against styrene ene oxide, we expressed the cDNA of hmEH in V79 7,8-oxide genotoxicity. On the other hand, no pro-Chinese hamster cells. We obtained a number of tective effect of epoxide hydrolase expression could cell clones that expressed functionally active epox-be observed on ethylene oxide-induced DNA damide hydrolase. Among these, the clone 92hmEH-age with the recombinant cell line over a dose V79 revealed an especially high enzymatic mEH range of 0.5-2.5 mM ethylene oxide. This selectivactivity toward styrene 7,8-oxide (10 nmol con-ity of the protective effect on epoxide genotoxicity verted per mg of protein per min, measured in the thus appears to be an important factor that must be 9.000 1 g supernatant of the cell homogenate), taken into account for the prediction of the genothat was 100 times higher than that determined in toxic risk of epoxides themselves or compounds that mock-transfected cells and within the range of mEH can be metabolically activated to epoxides. Enviactivity in human liver. Styrene 7,8-oxide-induced ron. Mol. Mutagen. 30:429-439, 1997 DNA single-strand breaks/alkali labile sites (dose ᭧ 1997 Wiley-Liss, Inc.