Glutathione S-transferase-mediated mutagenicity of trihalomethanes in Salmonella typhimurium: Contrasting results with bromodichloromethane and chloroform
Glutathione S-transferase-mediated mutagenicity of trihalomethanes in Salmonella typhimurium: Contrasting results with bromodichloromethane and chloroform
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DOI：
10.1006/taap.1997.8123
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发表时间：
1997-05-01
影响因子：
3.8
通讯作者：
Claxton, LD
中科院分区：
文献类型：
--
作者：
Pegram, RA;Andersen, ME;Claxton, LD
三卤甲烷（THMs）是氯化饮用水中最常见的消毒副产物。在THMs中，氯仿（CHCl 3）通常以最高浓度出现在成品水中，但是溴化THMs（CHBrCl 2、CHBr 2Cl和CHBr 3）中的每一种的浓度可以超过CHCl 3的浓度。在长期口服给药研究中，这四种THM中的每一种都对啮齿动物具有致癌性。本研究评估了THM在用大鼠θ类谷胱甘肽S-转移酶T1-1（+GST）转染的鼠伤寒沙门氏菌TA 1535菌株中的致突变性。将+GST菌株及其未转染的亲本菌株（-GST）用于平板掺入试验，并在密封的Tedlar袋中暴露于浓度高达25，600 ppm的单个THMs蒸汽中24小时。碱基置换回复突变体中产生的+GST菌株在剂量依赖性的方式CHBrCl 2，但不是由CHCl 3。在4800 ppm CHBrCl 2（产生0.67 mM的计算琼脂浓度）下，每个平板有419 +/- 75个回复突变体，而自发水平为23 +/- 5。CHCl 3仅在两个最高检测浓度（19，200和25，600 ppm）下产生加倍的回复突变体。这些结果表明，溴化的THMs赋予的能力θ类GST介导的转化致突变的中间体在低底物浓度，这表明在人类中类似的激活途径的可能性。此外，GSH依赖性途径对CHCl 3的亲和力非常低，这表明不同的THMs可以通过不同的机制诱导不良反应，这表明THMs的风险评估不应将此类成员视为具有共同的作用模式。(C)北京：科学出版社.
Trihalomethanes (THMs) are the most prevalent disinfection by-products identified in chlorinated drinking water. Among the THMs, chloroform (CHCl3) generally occurs at the highest concentration in finished water, but the concentrations of each of the brominated THMs (CHBrCl2, CHBr2Cl, and CHBr3) can exceed that of CHCl3. Each of these four THMs was carcinogenic in rodents in chronic oral dosing studies, This study assessed THM mutagenicity in a strain of Salmonella typhimurium TA1535 that was transfected with rat theta-class glutathione S-transferase T1-1 (+GST). The +GST strain and its nontransfected parent strain (-GST) were employed in a plate-incorporation assay and exposed for 24 hr to the vapor of individual THMs at concentrations up to 25,600 ppm in sealed Tedlar bags. Base-substitution revertants were produced in the +GST strain in a dose-dependent fashion by CHBrCl2 but not by CHCl3. At 4800 ppm CHBrCl2, which produced a calculated agar concentration of 0.67 mM, there were 419 +/- 75 revertants per plate compared to a spontaneous level of 23 +/- 5. CHCl3 produced a doubling of revertants only at the two highest concentrations tested (19,200 and 25,600 ppm). These results indicate that bromination of THMs confers the capability for theta-class GST-mediated transformation to mutagenic intermediates at low substrate concentrations, suggesting the possibility of a similar activation route in humans. Further, the very low affinity of the GSH-dependent pathway for CHCl3 demonstrates that different THMs can induce adverse effects via different mechanisms, indicating that risk evaluations of THMs should not treat members of this class as if they shared a common mode of action. (C) 1997 Academic Press.