Simon P, Epe B, Mützel P, Schiffmann D, Wild D, Ottenwälder H, Fedtke N, Bolt H M, Henschler D
Institut für Arbeitsphysiologie an der Universität Dortmund, FRG.
J Biochem Toxicol. 1986 Jun;1(2):43-55. doi: 10.1002/jbt.2570010205.
Acetoxyoxirane, the epoxide of vinyl acetate and a potential reactive intermediate, was synthesized and characterized by 13C-nuclear magnetic resonance (13C-NMR) and mass spectroscopy. The compound induced lesions (endonuclease-sensitive and alkali-labile sites) in supercoiled PM2 DNA in vitro and was directly mutagenic toward Salmonella typhimurium TA100. The mutagenicity of the epoxide in phosphate buffer (pH 7.4, 37 degrees C) decreased, with an initial half-life of 2.8 minutes, and mutagenicity was completely abolished by addition of S-9 mix. Acetoxyoxirane did not induce unscheduled DNA synthesis on incubation with Syrian hamster embryo fibroblasts (SHE cells). These findings may possibly be explained by an effective inactivation of acetoxyoxirane by esterases when these are present in the biological system. This view is consistent with the lack of acetoxyoxirane detected in rat liver microsomal incubations of vinyl acetate.
乙酸氧基环氧乙烷是醋酸乙烯酯的环氧化物，也是一种潜在的反应中间体，已通过碳-13核磁共振（13C-NMR）和质谱法进行了合成和表征。该化合物在体外能诱导超螺旋PM2 DNA产生损伤（核酸内切酶敏感位点和碱不稳定位点），并且对鼠伤寒沙门氏菌TA100具有直接致突变性。该环氧化物在磷酸盐缓冲液（pH 7.4，37℃）中的致突变性降低，初始半衰期为2.8分钟，加入S-9混合物后致突变性完全消除。乙酸氧基环氧乙烷与叙利亚仓鼠胚胎成纤维细胞（SHE细胞）孵育时不会诱导非程序性DNA合成。当生物系统中存在酯酶时，这些发现可能可以通过乙酸氧基环氧乙烷被酯酶有效灭活来解释。这一观点与在醋酸乙烯酯的大鼠肝微粒体孵育中未检测到乙酸氧基环氧乙烷一致。
