Division of Analytical & Environmental Toxicology, Department of Laboratory Medicine & Pathology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
Division of Analytical & Environmental Toxicology, Department of Laboratory Medicine & Pathology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada; Alberta Centre for Toxicology, Department of Physiology & Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
J Environ Sci (China). 2017 Aug;58:239-249. doi: 10.1016/j.jes.2017.02.006. Epub 2017 Feb 20.
Human neural stem cells (hNSCs) are a useful tool to assess the developmental effects of various environmental contaminants; however, the application of hNSCs to evaluate water disinfection byproducts (DBPs) is scarce. Comprehensive toxicological results are essential to the prioritization of DBPs for further testing and regulation. Therefore, this study examines the effects of DBPs on the proliferation and differentiation of hNSCs. Prior to DBP treatment, characteristic protein markers of hNSCs from passages 3 to 6 were carefully examined and it was determined that hNSCs passaged 3 or 4 times maintained stem cell characteristics and can be used for DBP analysis. Two regulated DBPs, monobromoacetic acid (BAA) and monochloroacetic acid (CAA), and two emerging DBPs, 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ) and 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), were chosen for hNSC treatment. Both 2,6-DBBQ and 2,6-DCBQ induced cell cycle arrest at S-phase at concentrations up to 1μmol/L. Comparatively, BAA and CAA at 0.5μmol/L affected neural differentiation. These results suggest DBP-dependent effects on hNSC proliferation and differentiation. The DBP-induced cell cycle arrest and inhibition of normal hNSC differentiation demonstrate the need to assess the developmental neurotoxicity of DBPs.
人神经干细胞（hNSCs）是评估各种环境污染物发育效应的有用工具；然而，将 hNSCs 应用于评估水消毒副产物（DBPs）的研究还很少。全面的毒理学结果对于将 DBPs 优先用于进一步测试和监管是至关重要的。因此，本研究考察了 DBPs 对 hNSCs 增殖和分化的影响。在 DBP 处理之前，仔细检查了第 3 至 6 代 hNSCs 的特征蛋白标志物，并确定传代 3 或 4 次的 hNSCs 保持干细胞特征，可用于 DBP 分析。选择了两种受管制的 DBPs，单溴乙酸（BAA）和单氯乙酸（CAA），以及两种新兴的 DBPs，2,6-二溴-1,4-苯醌（2,6-DBBQ）和 2,6-二氯-1,4-苯醌（2,6-DCBQ）用于 hNSC 处理。在浓度高达 1μmol/L 时，2,6-DBBQ 和 2,6-DCBQ 均诱导 S 期细胞周期停滞。相比之下，BAA 和 CAA 在 0.5μmol/L 时影响神经分化。这些结果表明 DBP 对 hNSC 增殖和分化有依赖性影响。DBP 诱导的细胞周期停滞和正常 hNSC 分化的抑制表明需要评估 DBPs 的发育神经毒性。
