Biomolecular and Computational Toxicology Division, Center for Computational Toxicology and Exposure, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
863 Fox St, Denver, Colorado, USA.
Environ Mol Mutagen. 2021 Mar;62(3):168-176. doi: 10.1002/em.22423. Epub 2021 Feb 15.
Drinking water disinfection by-products (DBPs), including the ubiquitous trihalomethanes (THMs), are formed during the treatment of water with disinfectants (e.g., chlorine, chloramines) to produce and distribute potable water. Brominated THMs (Br-THMs) are activated to mutagens via glutathione S-transferase theta 1 (GSTT1); however, iodinated THMs (I-THMs) have never been evaluated for activation by GSTT1. Among the I-THMs, only triiodomethane (iodoform) has been tested previously for mutagenicity in Salmonella and was positive (in the absence of GSTT1) in three strains (TA98, TA100, and BA13), all of which have error-prone DNA repair (pKM101). We evaluated five I-THMs (chlorodiiodomethane, dichloroiodomethane, dibromoiodomethane, bromochloroiodomethane, and triiodomethane) for mutagenicity in Salmonella strain RSJ100, which expresses GSTT1, and its homologue TPT100, which does not; neither strain has pKM101. We also evaluated chlorodiiodo-, dichloroiodo-, and dibromoiodo-methanes in strain TA100 +/- rat liver S9 mix; TA100 has pKM101. None was mutagenic in any of the strains. The I-THMs were generally more cytotoxic than their brominated and chlorinated analogues but less cytotoxic than analogous trihalonitromethanes tested previously. All five I-THMs showed similar thresholds for cytotoxicity at ~2.5 μmoles/plate, possibly due to release of iodine, a well-known antimicrobial. Although none of these I-THMs was activated by GSTT1, iodoform appears to be the only I-THM that is mutagenic in Salmonella, only in strains deficient in nucleotide excision repair (uvrB) and having pKM101. Given that only iodoform is mutagenic among the I-THMs and is generally present at low concentrations in drinking water, the I-THMs likely play little role in the mutagenicity of drinking water.
饮用水消毒副产物（DBPs），包括普遍存在的三卤甲烷（THMs），是在使用消毒剂（如氯、氯胺）处理水以生产和分配饮用水时形成的。溴代三卤甲烷（Br-THMs）通过谷胱甘肽 S-转移酶 theta 1（GSTT1）被激活为致突变物；然而，碘代三卤甲烷（I-THMs）从未被评估过 GSTT1 的激活作用。在 I-THMs 中，只有三碘甲烷（碘仿）以前在沙门氏菌中进行过致突变性测试，并且在三个菌株（TA98、TA100 和 BA13）中均为阳性（没有 GSTT1），这三个菌株均具有易错 DNA 修复（pKM101）。我们评估了五种 I-THMs（氯二碘甲烷、二氯碘甲烷、二溴碘甲烷、溴氯碘甲烷和三碘甲烷）在表达 GSTT1 的沙门氏菌菌株 RSJ100 及其同源物 TPT100 中的致突变性，后者没有 pKM101。我们还评估了氯二碘、二氯碘和二溴碘甲烷在菌株 TA100 +/-大鼠肝 S9 混合物中的致突变性；TA100 有 pKM101。在任何菌株中，这些 I-THMs 都没有致突变性。I-THMs 的细胞毒性通常比其溴代和氯代类似物更强，但比以前测试的类似三卤硝基甲烷的细胞毒性更小。五种 I-THMs 在约 2.5 μmoles/板的细胞毒性阈值上表现出相似性，这可能是由于碘的释放，碘是一种众所周知的抗菌剂。尽管这些 I-THMs 都没有被 GSTT1 激活，但碘仿似乎是唯一在沙门氏菌中具有致突变性的 I-THM，仅在核苷酸切除修复（uvrB）缺陷且具有 pKM101 的菌株中。鉴于 I-THMs 中只有碘仿具有致突变性，并且通常在饮用水中的浓度较低，因此 I-THMs 在饮用水的致突变性中可能作用不大。
