PMID: 9438519Jan 23, 1998Paper

Cytochrome P-4502E1-dependent formation of trifluoroacetyl adducts from halothane by transduced HepG2 cells

Alcoholism, Clinical and Experimental Research
D E Feierman, Z Melnikov

Abstract

E-9 cells, a HepG2 cell line that has the alcohol-inducible human cytochrome P-4502E1 (CYP2E1) cloned into its genome, was tested for its ability to produce trifluoroacetyl (TFA) adducts from the metabolism of halothane. The metabolism of halothane results in the production of TFA halide that can readily react with cellular proteins to form TFA adducts, which can be detected by antibodies directed against them. E-9 cells formed TFA adducts when incubated with halothane. The major consistent bands that were detected were of molecular weights of approximately 50, 78, and 100 kDa. The formation of these adducts was dependent on halothane concentration and time of incubation with halothane. MV-5 cells, the control cell line that has the viral vector without the P-450, did not produce any adducts. Inhibitors of CYP2E1 function, such as 4-methylpyrazole, inhibited adduct formation. Furthermore, phorbol esters, which have been shown to increase the CYP2E1 level in this cell line, increased TFA adduct formation. This HepG2 cell line may be of value in studying the metabolism and toxicity of halothane in a human cell culture model.

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Citations

Jan 29, 2002·Archives of Biochemistry and Biophysics·D E FeiermanJ Zhang
Mar 31, 2005·Archives of Biochemistry and Biophysics·Martin D Lewis, Ben J Roberts
Mar 8, 2005·Drug Metabolism Reviews·Shufeng ZhouYu-Zong Chen
Oct 4, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Xiao-Xia YangShu-Feng Zhou
Jan 6, 2001·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·D J NaisbittB K Park

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