Krause R J, Sharer J E, Elfarra A A
Department of Comparative Biosciences and Environmental Toxicology Center, University of Wisconsin-Madison 53706, USA.
Drug Metab Dispos. 1997 Aug;25(8):1013-5.
Incubations of butadiene monoxide (BMO) with mouse, rat, and human liver microsomes or cDNA-expressed human microsomal epoxide hydrolase led to 3-buten-1,2-diol (BDD) detection; the BDD peak exhibited a GC/MS fragmentation pattern similar to that of reference material. Incubations with rat liver cytosol did not lead to BDD detection; however, when mouse or human liver cytosol was used, BDD was detected but at levels lower than those detected with the liver microsomes. The catalytic efficiency (V(max)/K(m) ratio) of BDD formation in rat liver microsomes was nearly 3-fold higher than the ratio obtained with mouse liver microsomes. Among two human liver microsomal samples, one sample exhibited a ratio that was nearly 3-fold higher than that of rat liver microsomes, and the second sample exhibited a ratio that was similar to that of rat liver microsomes. Although these results suggest epoxide hydrolases may play a role in BMO metabolism in vivo, rats and mice given BMO (71.3-285 micromol/kg) excreted <1% of the dose as BDD into urine within 24 hr. Thus, further studies into the role of epoxide hydrolases in BMO metabolism and disposition and the fate of BDD are warranted.
将一氧化二丁烯（BMO）与小鼠、大鼠和人肝脏微粒体或cDNA表达的人微粒体环氧化物水解酶一起温育，可检测到3-丁烯-1,2-二醇（BDD）；BDD峰呈现出与参考物质相似的气相色谱/质谱碎片模式。用大鼠肝脏胞液温育未检测到BDD；然而，当使用小鼠或人肝脏胞液时，可检测到BDD，但水平低于用肝脏微粒体检测到的水平。大鼠肝脏微粒体中BDD形成的催化效率（V(max)/K(m)比值）比小鼠肝脏微粒体获得的比值高近3倍。在两个人肝脏微粒体样品中，一个样品的比值比大鼠肝脏微粒体高近3倍，另一个样品的比值与大鼠肝脏微粒体相似。虽然这些结果表明环氧化物水解酶可能在体内BMO代谢中起作用，但给予BMO（71.3 - 285微摩尔/千克）的大鼠和小鼠在24小时内将<1%的剂量以BDD形式排泄到尿液中。因此，有必要进一步研究环氧化物水解酶在BMO代谢和处置中的作用以及BDD的去向。
