新型饮用水消毒副产物卤代苯醌的质谱多反应检测和遗传毒性研究

Halobenzoquinones (HBQs) are a new class of emerging unregulated disinfection by-product in drinking water. Quantitative structure toxicity relationship (QSTR) analysis predicted HBQs as plausible bladder carcinogens. However, there is little or no experimental data on the formation and carcinogenicity of these compounds. Thus, this study aims to carry out a comprehensive study on the formation of HBQs in drinking water of water plants of Nanning based on mass spectrometry multiple reaction monitoring (MRM) method. The relationship between water quality/treatment/distribution and HBQs formation will be investigated. The predictive models for HBQs formation and transformation will be made based on these surveillance data. The genotoxicity of HBQs will be evaluated by a battery of genetic bioassays covering gene mutation, DNA damage, and chromosome aberration. The potential carcinogenicity of HBQs will be determined by cell transformation assay in vitro. Further, the role of Nrf2- Keap1- ARE pathway in the toxical mechanism will be studied. The data obtained will be valuable to water suppliers for water treatment optimization and HBQs control. It will be also helpful to provide evidence for the establishment of standard for drinking water quality.

卤代苯醌（HBQs）是饮用水中新现的一类未受控消毒副产物，结构定量毒性关系模型分析可能是膀胱癌致癌物，然而目前不仅对HBQs的形成还是致癌性均缺乏直接实验数据。故本研究基于质谱多反应检测（MRM）技术，对南宁市饮用水中HBQs的状况进行调查，研究水源水质、制水工艺、消毒剂种类和管网输送对HBQs形成的影响，并构建HBQs生成和转归预测模型。继而通过一套反映基因突变、DNA损伤和染色体断裂等多遗传终点的毒性测试组合方法以及体外细胞恶性转化试验对HBQs的遗传毒性和潜在致癌性进行评估，并从Nrf2- Keap1- ARE通路探讨其作用机制。研究结果将为水厂自来水加工工艺优化升级、HBQs的过程控制和制定饮用水水质卫生标准提供科学依据。

卤代苯醌（HBQs）是饮用水中新现的一类未受控消毒副产物，结构定量毒性关系模型分析可能是膀胱癌致癌物，然而目前不仅对HBQs的形成还是致癌性均缺乏直接实验数据。故本研究在建立质谱多反应检测（MRM）技术基础上，对南宁市饮用水中HBQs的状况进行调查，研究水源水质、制水工艺、消毒剂种类和管网输送对HBQs形成的影响，并构建HBQs生成和转归预测模型。继而通过一套反映基因突变、DNA损伤和染色体断裂等多遗传终点的毒性测试组合方法以及体外细胞恶性转化试验对HBQs的遗传毒性和潜在致癌性进行评估。本研究结果显示，建立的基于MRM质谱技术检测饮用水中HBQs的方法具有分离效果好，灵敏度高，稳定性好，定性定量准确，操作较简单的特点。采用该法在水厂出厂水和管网末稍水中检出2,6-DCBQ、2,6-DBBQ和TetraC-1,2-BQ，含量为＜0.38~19.7 ng/L。高余氯有利于出厂水HBQs的形成；高余氯、低钙离子浓度有利于末梢水HBQs的形成。随着管网输送距离的增加，饮用水HBQs含量降低。同时，游泳池水也检出2,6-DCBQ、2,6-DBBQ和TetraC-1,2-BQ，含量为＜0.38~45.3 ng/L。泳池水2,6-DCBQ和总HBQs浓度高于注入泳池的自来水。泳池水总HBQs浓度与腐植酸和氯离子浓度呈正相关关系，与钙离子浓度呈负相关关系。通过HPRT基因突变试验检测9种HBQs位点突变情况结果呈阴性；通过单细胞凝胶电泳试验检测9种HBQs原始DNA损伤效应发现2,6-DCBQ和2,5-DCBQ出现弱阳性结果；通过胞质阻滞法微核试验检测9种HBQs染色体损伤作用发现，除2,5-DBBQ和2,3-DIBQ 外，其余7种HBQs具有致染色体损伤作用。结合以上3项遗传毒性试验结果表明HBQs为可疑遗传毒物。此外，2,6-DCBQ可诱导NIH3T3细胞发生恶性转化，表明其可能具有潜在致癌性。研究结果将为水厂自来水加工工艺优化升级、HBQs的过程控制和制定饮用水水质卫生标准提供科学依据。