硫芥（1,1'-硫代双（2-氯乙烷））的生物归宿：人尿中β-裂解酶代谢产物和水解产物的鉴定

Biological fate of sulphur mustard, 1,1'-thiobis(2-chloroethane): identification of beta-lyase metabolites and hydrolysis products in human urine.

Black R M, Read R W

Chemical and Biological Defence Establishment, Porton Down, Salisbury, UK.

Xenobiotica. 1995 Feb;25(2):167-73. doi: 10.3109/00498259509061842.

Abstract

Samples of urine from two human subjects accidentally exposed to sulphur mustard were analysed for metabolites derived from hydrolysis (thiodiglycol, thiodiglycol sulphoxide), conjugation with glutathione (1,1'-sulphonylbis [2-S-(N-acetylcysteinyl)ethane]) and from further metabolism of glutathione conjugates by the beta-lyase pathway (1,1-sulphonylbis[2-(methylsulphinyl)ethane], 1-methylsulphinyl-2-[2-(methylthio)ethylsulphonyl]ethane). 2. Thiodiglycol sulphoxide was excreted in much higher concentrations than thiodiglycol, as was observed previously in rat exposed to sulphur mustard. However, the use of thiodiglycol sulphoxide as a biological marker for sulphur mustard poisoning is limited by its presence at low concentrations in normal human urine. 3. beta-lyase metabolites were detected at concentrations comparable with those of thiodiglycol sulphoxide. No background levels of beta-lyase metabolites have been detected in normal human urine, and they are proposed as unequivocal diagnostic and forensic indicators of sulphur mustard poisoning in man.

摘要

对两名意外接触硫芥的人类受试者的尿液样本进行了分析，以检测水解代谢产物（硫代二甘醇、硫代二甘醇亚砜）、与谷胱甘肽结合的产物（1,1'-磺酰基双[2-S-(N-乙酰半胱氨酰基)乙烷]）以及谷胱甘肽结合物经β-裂解酶途径进一步代谢的产物（1,1-磺酰基双[2-(甲基亚磺酰基)乙烷]、1-甲基亚磺酰基-2-[2-(甲硫基)乙基磺酰基]乙烷）。2. 硫代二甘醇亚砜的排泄浓度远高于硫代二甘醇，这与之前在接触硫芥的大鼠中观察到的情况相同。然而，硫代二甘醇亚砜作为硫芥中毒生物标志物的应用受到其在正常人尿液中浓度较低的限制。3. 检测到的β-裂解酶代谢产物浓度与硫代二甘醇亚砜相当。在正常人尿液中未检测到β-裂解酶代谢产物的背景水平，因此它们被提议作为人类硫芥中毒明确的诊断和法医指标。