Wang Wei, Qian Yichao, Li Jinhua, Moe Birget, Huang Rongfu, Zhang Hongquan, Hrudey Steve E, Li Xing-Fang
Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta , Edmonton, Alberta T6G 2G3, Canada.
Anal Chem. 2014 May 20;86(10):4982-8. doi: 10.1021/ac5007238. Epub 2014 May 7.
Exposure to chlorination disinfection byproducts (DBPs) is potentially associated with an increased risk of bladder cancer. Four halobenzoquinones (HBQs) have been detected in treated drinking water and have shown potency in producing reactive oxygen species and inducing damage to cellular DNA and proteins. These HBQs are unstable in drinking water. The fate and behavior of these HBQs in drinking water distribution systems is unclear. Here we report the high-resolution mass spectrometry identification of the transformation products of HBQs as halo-hydroxyl-benzoquinones (OH-HBQs) in water under realistic conditions. To further examine the kinetics of transformation, we developed a solid-phase extraction with ultrahigh-performance liquid chromatography tandem mass spectrometry (SPE-UHPLC-MS/MS) method to determine both the HBQs and OH-HBQs. The method provides reproducible retention times (SD < 0.05 min), limits of detection (LODs) at subnanogram per liter levels, and recoveries of 68%-96%. Using this method, we confirmed that decrease of HBQs correlated with increase of OH-HBQs in both the laboratory experiments and several distribution systems, supporting that OH-HBQs were more stable forms of HBQ DBPs. To understand the toxicological relevance of the OH-HBQs, we studied the in vitro toxicity with CHO-K1 cells and determined the IC50 of HBQs and OH-HBQs ranging from 15.9 to 72.9 μM. While HBQs are 2-fold more toxic than OH-HBQs, both HBQs and OH-HBQs are substantially more toxic than the regulated DBPs.
接触氯化消毒副产物（DBPs）可能会增加患膀胱癌的风险。在处理后的饮用水中已检测到四种卤代苯醌（HBQs），它们在产生活性氧以及诱导细胞DNA和蛋白质损伤方面表现出活性。这些HBQs在饮用水中不稳定。它们在饮用水分配系统中的归宿和行为尚不清楚。在此，我们报告了在实际条件下水中HBQs转化产物卤代羟基苯醌（OH-HBQs）的高分辨率质谱鉴定。为了进一步研究转化动力学，我们开发了一种固相萃取结合超高效液相色谱串联质谱（SPE-UHPLC-MS/MS）方法来测定HBQs和OH-HBQs。该方法提供了可重现的保留时间（SD < 0.05分钟）、纳克每升水平的检测限（LODs）以及68%-96%的回收率。使用该方法，我们在实验室实验和几个分配系统中均证实HBQs的减少与OH-HBQs的增加相关，这支持了OH-HBQs是HBQ DBPs更稳定形式的观点。为了了解OH-HBQs的毒理学相关性，我们用CHO-K1细胞研究了体外毒性，并确定了HBQs和OH-HBQs的半数抑制浓度（IC50）范围为15.9至72.9 μM。虽然HBQs的毒性比OH-HBQs高2倍，但HBQs和OH-HBQs的毒性均远高于受监管的DBPs。
