N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine and 2,2,2-trichloroethanol: two novel metabolites of tetrachloroethene in humans after occupational exposure.
N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine and 2,2,2-trichloroethanol: two novel metabolites of tetrachloroethene in humans after occupational exposure.
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N-乙酰基-S-(1,2,2-三氯乙烯基)-L-半胱氨酸和2,2,2-三氯乙醇：职业接触后人体四氯乙烯的两种新代谢物。
DOI：
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发表时间：
1996
影响因子：
3.9
通讯作者：
W. Dekant
中科院分区：
文献类型：
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作者：
G. Birner;A. Rutkowska;W. Dekant
本文研究了职业接触工人尿中四氯乙烯代谢物的排泄，以鉴定和定量人体内谷胱甘肽结合和细胞色素P450氧化四氯乙烯所形成的代谢物。谷胱甘肽结合途径与四氯乙烯对大鼠肾脏的慢性毒性和可能的致瘤性有关。S-(1，2，2-三氯乙烯基)谷胱甘肽和N-乙酰基-S-(1，2，2-三氯乙烯基)-L-半胱氨酸在人体内的生物合成未见报道。在这项研究中，我们调查了在干洗过程中职业暴露的人中四氯乙烯的生物转化。干洗店空气中四氯乙烯浓度为50+/-4ppm；两个人每天接触8小时，两个人每天接触4小时。用GC/MS法对人体内四氯乙烯代谢物N-乙酰基-S-(1，2，2-三氯乙烯)-L-半胱氨酸和2，2，2-三氯乙醇进行了鉴定，发现N-乙酰基-S-(1，2，2-三氯乙烯)-L-半胱氨酸在工作周开始和结束时无显著差异；然而，作为细胞色素P450代谢标志物的N-乙酰基-S-(1，2，2-三氯乙烯)-L半胱氨酸和2，2，2-三氯化合物(三氯乙酸和2，2，2-三氯乙醇)的浓度与每天接触四氯乙烯的时间成正比。主要的四氯乙烯代谢物2，2，2-三氯化合物的排泄模式有显著差异。其中两名接触者的尿液中含有三氯乙酸和2，2，2-三氯乙醇。在另外两个没有排泄可检测到的三氯乙酸量的人中，只有2，2，2-三氯乙醇被鉴定为主要的尿四氯乙烯代谢物。结果表明，人也具有从四氯乙烯生物合成肾毒性谷胱甘肽S偶联物的能力，但与大鼠相比，人合成N-乙酰基-S-(1，2，2-三氯乙烯)-L-半胱氨酸的能力似乎较低。
The excretion of tetrachloroethene metabolites in urine was studied in occupationally exposed workers to identify and quantify metabolites formed by glutathione conjugation and by cytochrome P450 oxidation of tetrachloroethene in humans. The glutathione conjugation pathway has been implicated in the chronic toxicity and possible tumorigenicity of tetrachloroethene to the kidney in rats. The biosynthesis of S-(1,2,2-trichlorovinyl)glutathione and N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine in humans had not been demonstrated. In this study, we investigated the biotransformation of tetrachloroethene in humans occupationally exposed during dry cleaning. Tetrachloroethene concentrations in the air of the dry cleaning shop were 50 +/- 4 ppm; two individuals were exposed for 8 hr daily and two individuals were exposed for 4 hr daily. In urine samples collected from the individuals at the beginning and at the end of the work week, N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine and 2,2,2-trichloroethanol as tetrachloroethene metabolites in humans were identified by GC/MS. The concentrations of N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine in the urine of the individuals were not significantly different at the start and at the end of the work week; however, concentrations of both N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine and 2,2,2-trichloro compounds (trichloroacetic acid and 2,2,2-trichloroethanol) as a marker for cytochrome P450-mediated metabolism were proportional to the length of daily tetrachloroethene exposure. A remarkable difference in the excretion pattern of 2,2,2-trichloro compounds, the major tetrachloroethene metabolites, was observed. Trichloroacetic acid and 2,2,2-trichloroethanol were present in the urine of two of the exposed individuals. Only 2,2,2-trichloroethanol was identified as a major urinary tetrachloroethene metabolite in two other individuals who did not excrete detectable amounts of trichloroacetic acid. The obtained results indicate that humans also have the ability to biosynthesize nephrotoxic glutathione S-conjugates from tetrachloroethene; however, when compared with rats, the human capacity for the biosynthesis of N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine seems to be lower.