Kargalioglu Yahya, McMillan Brian J, Minear Roger A, Plewa Michael J
Department of Crop Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Teratog Carcinog Mutagen. 2002;22(2):113-28. doi: 10.1002/tcm.10010.
We analyzed the cytotoxicity and mutagenicity of the drinking water disinfection by-products (DBPs) bromoform (BF), bromoacetic acid (BA), dibromoacetic acid (DBA), tribromoacetic acid (TCA), chloroform (CF), chloroacetic acid (CA), dichloroacetic acid (DCA), trichloroacetic acid (TCA), 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), and potassium bromate (KBrO3) in Salmonella typhimurium strains TA98, TA100, and RSJ100 +/- S9. Solvent controls of DMSO and ethanol and a positive control of ethylmethanesulfonate (EMS) were also analyzed. We developed a rapid microplate-based method to determine the cytotoxicity of the DBPs and we determined their mutagenic potencies. The distributions of the rank order for the cytotoxicity and mutagenicity of these DBPs were compared and the structure-function relationships were identified. TA100 -S9 was the most sensitive strain for these DBPs. The rank order of the mutagenic potency adjusted with a cytoxicity factor was MX > BA > EMS > DBA > DCA > CA with TBA, TCA, BF, and CF not mutagenic. From a structure-function perspective, the brominated acetic acids were more cytotoxic and mutagenic than their chlorinated analogs. BA was 150x more mutagenic than CA. The mutagenic potency of the haloacetic acids was inversely related to the number of halogen atoms of the molecule. BA was 36x more mutagenic than DBA. The differential cytotoxicity expressed by the DBPs indicated that a cytotoxicity analysis enhanced the sensitivity of the mutagenicity data, which resulted in an enhanced precision for comparing their relative mutagenic strengths. This information is critical when conducting quantitative structure-function analysis of these hazardous agents.
我们分析了饮用水消毒副产物（DBPs）溴仿（BF）、溴乙酸（BA）、二溴乙酸（DBA）、三溴乙酸（TCA）、氯仿（CF）、氯乙酸（CA）、二氯乙酸（DCA）、三氯乙酸（TCA）、3 - 氯 - 4 -（二氯甲基）- 5 - 羟基 - 2[5H] - 呋喃酮（MX）和溴酸钾（KBrO₃）在鼠伤寒沙门氏菌TA98、TA100和RSJ100 +/- S9菌株中的细胞毒性和致突变性。还分析了二甲基亚砜（DMSO）和乙醇的溶剂对照以及甲磺酸乙酯（EMS）的阳性对照。我们开发了一种基于微孔板的快速方法来测定DBPs的细胞毒性，并确定它们的致突变潜力。比较了这些DBPs细胞毒性和致突变性的排名顺序分布，并确定了结构 - 功能关系。TA100 - S9是对这些DBPs最敏感的菌株。用细胞毒性因子调整后的致突变潜力排名顺序为MX > BA > EMS > DBA > DCA > CA，其中TBA、TCA、BF和CF无致突变性。从结构 - 功能角度来看，溴代乙酸比其氯代类似物具有更高的细胞毒性和致突变性。BA的致突变性比CA高150倍。卤代乙酸的致突变潜力与分子中的卤原子数量呈负相关。BA比DBA的致突变性高36倍。DBPs表现出的不同细胞毒性表明，细胞毒性分析提高了致突变性数据的敏感性，从而提高了比较它们相对致突变强度的精度。在对这些有害物质进行定量结构 - 功能分析时，这些信息至关重要。
