Birner G, Vamvakas S, Dekant W, Henschler D
Institut für Toxikologie, Universität Würzburg, Federal Republic of Germany.
Environ Health Perspect. 1993 Mar;99:281-4. doi: 10.1289/ehp.9399281.
Excretion of mercapturic acids in the urine is indicative of the formation of electrophiles in the metabolism of xenobiotics. The determination of these mercapturic acids thus may be a useful method to estimate the exposure. We identified the nephrotoxic and mutagenic mercapturic acids N-acetyl-S-(1,2-dichlorovinyl)-L- cysteine and N-acetyl-S-(2,2-dichlorovinyl)-L-cysteine in the urine of workers exposed to 1,1,2-trichloroethene. A method to quantify these mercapturic acids by gas chromatography-mass spectrometry-selected ion monitoring was developed and appreciable amounts (2.8-3.8 mumole/L were found in human urine samples. Because deacetylation determines notably the amount of the excreted mercapturic acids, the formation of the resulting cysteine S-conjugates was comparably measured in subcellular fractions of rodent and human kidneys; significant species differences in acylase activity were found. The formation of mutagenic and nephrotoxic metabolites during 1,1,2-trichloroethene metabolism mandates a revision of the risk assessment of trichloroethene exposure.
尿中硫醚氨酸的排泄表明在异生物代谢过程中亲电试剂的形成。因此，测定这些硫醚氨酸可能是评估暴露情况的一种有用方法。我们在接触1,1,2 - 三氯乙烯的工人尿液中鉴定出了具有肾毒性和致突变性的硫醚氨酸N - 乙酰 - S -（1,2 - 二氯乙烯基）- L - 半胱氨酸和N - 乙酰 - S -（2,2 - 二氯乙烯基）- L - 半胱氨酸。开发了一种通过气相色谱 - 质谱 - 选择离子监测来定量这些硫醚氨酸的方法，并且在人类尿液样本中发现了相当数量（2.8 - 3.8微摩尔/升）。由于脱乙酰作用显著决定了排泄的硫醚氨酸量，因此在啮齿动物和人类肾脏的亚细胞组分中对生成的半胱氨酸S - 共轭物的形成进行了比较测量；发现了酰基转移酶活性存在显著的物种差异。1,1,2 - 三氯乙烯代谢过程中致突变和肾毒性代谢物的形成要求对三氯乙烯暴露的风险评估进行修订。
