Molecular Toxicology Group, Department of Biology, University of Konstanz, 78457, Konstanz, Germany.
Molecular Toxicology Group, Department of Biology, University of Konstanz, 78457, Konstanz, Germany.
Toxicol Lett. 2018 Sep 1;293:21-30. doi: 10.1016/j.toxlet.2017.12.014. Epub 2017 Dec 23.
The bi-functional chemical warfare agent sulfur mustard (SM), whose release in asymmetric conflicts or terrorist attacks represents a realistic threat, induces several kinds of biomolecular adducts, including highly toxic DNA adducts. Isotope dilution liquid chromatographic tandem mass spectrometry (ID-LC-MS/MS) is considered the gold standard for highly accurate, precise, specific and sensitive quantification of DNA adducts in general. Recently, a number of LC-MS/MS approaches have been established to analyze SM-induced protein and DNA adducts in cell culture and rodent animal models. As DNA adducts are mechanism-based biomarkers for SM exposure, results from such studies provide a deeper understanding of the etiology of SM-induced pathologies, especially of long-term effects such as cancer formation. As a result, medical treatment of SM-exposed individuals might be improved. Yet, despite the progress that has been made during the last years, there is still a need for advanced methods of ID-LC-MS/MS for the detection and quantitation of SM adducts.
双功能化学战剂芥子气（SM），其在非对称冲突或恐怖袭击中的释放构成了现实威胁，会诱导多种生物分子加合物的形成，包括毒性很强的 DNA 加合物。同位素稀释液相色谱串联质谱法（ID-LC-MS/MS）被认为是一般 DNA 加合物的高度准确、精确、特异和敏感定量的金标准。最近，已经建立了许多 LC-MS/MS 方法来分析细胞培养和啮齿类动物模型中 SM 诱导的蛋白质和 DNA 加合物。由于 DNA 加合物是 SM 暴露的基于机制的生物标志物，这些研究的结果提供了对 SM 诱导的病理学，特别是癌症形成等长期效应的病因学的更深入理解。因此，可以改善对 SM 暴露个体的治疗。然而，尽管近年来取得了进展，但仍需要先进的 ID-LC-MS/MS 方法来检测和定量 SM 加合物。
