Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology; Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, CAS; High Magnetic Field Laboratory, Hefei Institutes of Physical Science, CAS, Hefei, Anhui 230031, PR China; University of Science and Technology of China, Hefei, Anhui 230026, PR China.
Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology; Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, CAS; High Magnetic Field Laboratory, Hefei Institutes of Physical Science, CAS, Hefei, Anhui 230031, PR China.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117122. doi: 10.1016/j.ecoenv.2024.117122. Epub 2024 Oct 2.
Disinfection by-products (DBPs) generated from water treatment have serious adverse effects on human health and natural ecosystems. However, research on the mutagenicity of DBPs with different chemical structures is still limited. In the present study, we compared the mutagenicity of 8 typical DBPs in human-hamster hybrid (A) cells and clarified the mechanisms involved. Our data displayed that the rank order for mutagenicity was as follows: iodoacetamide (IAcAm) > iodoacetonitrile (IAN) > iodoacetic acid (IAA) > bromoacetamide (BAcAm) ≈ bromoacetonitrile (BAN) > bromoacetic acid (BAA), which was confirmed by DNA double strand breaks and oxidative DNA damage. In contrast, bromoform (TBM) and iodoform (TIM) had minimal mutagenicity. The mutation spectrum analysis further revealed that IAN, IAcAm, and IAA could induce multilocus deletions in mammalian cells. Interestingly, nitrogenous DBPs (N-DBPs) and IAA were found to cause varying degrees of iron overload and lipid peroxidation, which was mediated by the activation of the Nrf2/HO-1 signaling pathway. Moreover, the presence of deferoxamine (DFO), an iron ion inhibitor, effectively reduced γ-H2AX and 8-OHdG induced by N-DBPs and IAA. These results indicated that the variations in genotoxicity among DBPs with different structures were associated with their ability to disrupt iron homeostasis. This study provided new insights into the mechanisms underlying the structure-dependent toxicity of DBPs and established a foundation for a more comprehensive understanding and intervention of the health risks associated with DBPs.
水处理产生的消毒副产物 (DBPs) 对人类健康和自然生态系统有严重的不良影响。然而，不同化学结构的 DBPs 的致突变性研究仍然有限。在本研究中，我们比较了 8 种典型 DBPs 在人仓鼠杂种 (A) 细胞中的致突变性，并阐明了相关机制。我们的数据显示，致突变性的顺序如下：碘乙酰胺 (IAcAm) > 碘乙腈 (IAN) > 碘乙酸 (IAA) > 溴乙酰胺 (BAcAm) ≈ 溴乙腈 (BAN) > 溴乙酸 (BAA)，这通过 DNA 双链断裂和氧化 DNA 损伤得到了证实。相比之下，三溴甲烷 (TBM) 和碘仿 (TIM) 的致突变性最小。突变谱分析进一步表明，IAN、IAcAm 和 IAA 可以诱导哺乳动物细胞中的多位点缺失。有趣的是，含氮 DBPs (N-DBPs) 和 IAA 被发现导致不同程度的铁过载和脂质过氧化，这是由 Nrf2/HO-1 信号通路的激活介导的。此外，铁离子抑制剂去铁胺 (DFO) 的存在可有效减少 N-DBPs 和 IAA 诱导的 γ-H2AX 和 8-OHdG。这些结果表明，不同结构的 DBPs 之间的遗传毒性差异与其破坏铁稳态的能力有关。本研究为深入了解结构依赖性 DBPs 毒性机制提供了新的见解，并为更全面地理解和干预 DBPs 相关健康风险奠定了基础。
