Title of article :
Characterization of Two Distinct Mechanisms for Induction of Apoptosis in Human Vascular Endothelial Cells
Author/Authors :
Grafe، Michael نويسنده , , Steinheider، Gerhard نويسنده , , Desaga، Ulrike نويسنده , , Warnecke، Christina نويسنده , , Lehmkuhr، Hans B. نويسنده , , Regitz، Vera نويسنده , , Zagrosek، نويسنده , , Hildebrandt، Alfred G. نويسنده , , Fleck، Eckart نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 1999
Abstract :
Acrylonitrile (AN) and acrylamide (AM) are commonly used in the synthesis of plastics and polymers. In rodents, AM and AN are metabolized to the epoxides glycidamide and cyanoethylene oxide, respectively. The aim of this study was to determine the role of cytochrome P450 in the metabolism of AM and AN in vivo. Wild-type (WT) mice, WT mice pretreated with aminobenzotriazole (ABT, 50 mg/kg ip, 2 h pre-exposure), and mice devoid of cytochrome P450 2E1 (P450 2E1-null) were treated with 50 mg/kg PC]AM po. WT mice and P450 2EI-null mice were treated with 2.5 or 10 mg/kg [13C]AN po. Urine was collected for 24 h, and metabolites were characterized using 13C NMR. WT mice excreted metabolites derived from the epoxides and from direct GSH conjugation with AM or AN. Only metabolites derived from direct GSH conjugation with AM or AN were observed in the urine from ABT-pretreated WT mice and P450 2EI-null mice. On the basis of evaluation of urinary metabolites at these doses, these data suggest that P450 2EI is possibly the only cytochrome P450 enzyme involved in the metabolism of AM and AN in mice, that inhibiting total P450 activity does not result in new pathways ofnon-P450 metabolism of AM, and that mice devoid of P450 2EI do not excrete metabolites of AM or AN that would be produced by oxidation by other cytochrome P450s. P450 2EI-null mice may be an appropriate model for the investigation of the role ofoxidative metabolism in the toxicity or carcinogenicity of these compounds.
Keywords :
endothelium , Actinomycin-D. , Apoptosis
Journal title :
CLINICAL CHEMISTRY & LABORATORY MEDICINE
Journal title :
CLINICAL CHEMISTRY & LABORATORY MEDICINE