Formaldehyde (FA) is a human carcinogen that is ubiquitous in the ambient environment and also generated endogenously in oxidatively stressed cells. There is accumulated evidence that FA is an etiological agent of leukemia development in humans. To develop a biomarker for FA exposure, we have, in this study, developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with stable isotope-dilution method to explore the reactivity of FA with glutathione (GSH) in physiologically relevant conditions. Interestingly, analysis of the reaction mixture by LC-MS/MS revealed exposure concentration- and duration-dependent formation of thioproline-glycine (SPro-Gly) produced by reaction of FA with cysteinyl-glycine (Cys-Gly) as a novel metabolite. Furthermore, dose-dependent formation of the thioproline adduct was observed in human cells separately exposed to FA and Fe²⁺-EDTA, a hydroxyl radical source. To the best of our knowledge, this is the first study reporting a thiazolidine carboxylic acid formed by reaction of FA and Cys-Gly is a major metabolite of FA. The results suggest a variety of GSH-derived thiazolidine metabolites may serve as potential biomarkers for FA and oxidative stress exposure, and the developed LC-MS/MS method provides a means for accurate determination of SPro-Gly as a dosimeter of oxidative stress and formaldehyde exposure.

中文翻译：

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LC-MS / MS联用稳定同位素稀释法定量硫代脯氨酸-甘氨酸：甲醛和氧化应激暴露细胞中的新型代谢产物。

甲醛（FA）是人类致癌物，在周围环境中普遍存在，并且在氧化应激细胞中内源性产生。积累的证据表明，FA是人类白血病发展的病原体。为了开发FA暴露的生物标记，我们在这项研究中开发了液相色谱-串联质谱（LC-MS / MS）和稳定同位素稀释法，以探讨FA与谷胱甘肽（GSH）在生理上的反应性相关条件。有趣的是，通过LC-MS / MS对反应混合物的分析揭示了FA与半胱氨酰甘氨酸（Cys-Gly）反应生成的硫代脯氨酸-甘氨酸（SPro-Gly）的浓度和持续时间依赖性，这是一种新型代谢产物。此外，²⁺ -EDTA，羟基自由基源。据我们所知，这是第一项报道由FA与Cys-Gly反应形成的噻唑烷羧酸是FA的主要代谢产物的研究。结果表明，多种GSH衍生的噻唑烷代谢物可作为FA和氧化应激暴露的潜在生物标志物，并且已开发的LC-MS / MS方法提供了一种准确测定SPro-Gly作为氧化应激和甲醛剂量的方法。接触。