Abstract：
Intensified sanitation practices amid the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak might result in the increased release of chloramine disinfectants into surface water, significantly promoting the formation of nitrosamine disinfection by-products (DBPs) in drinking water. Unfortunately, these nitrosamine DBPs exhibit significant genotoxic, carcinogenic, and mutagenic properties, whereas chlorinating disinfectants remain in global practice. The current review provides valuable insights into the occurrence, identification, contamination status, exposure limits, and toxicity of the new unregulated disinfection by-products (nitrosamine DBPs) in drinking water. As a result, concentrations of nitrosamine DBPs far exceed allowable limits in drinking water, and prolonged exposure has the potential to cause metabolic disorders, a critical step in tumor initiation and progression. Importantly, based on recent research, we have concluded the role of nitrosamines DBPs in different metabolic pathways. Remarkably, nitrosamine DBPs can induce chronic inflammation and initiate tumors by activating sphingolipid and polyunsaturated fatty acid metabolism. Regarding amino acid and nucleotide metabolism, nitrosamine DBPs can inhibit tryptophan metabolism and de novo nucleotide synthesis. Moreover, inhibition of de novo nucleotide synthesis fails to repair DNA damage induced by nitrosamines. Additionally, the accumulation of lactate induced by nitrosamine DBPs may act as a pivotal signaling molecule in communication within the tumor microenvironment. However, with the advancement of tumor metabolomics, understanding the role of nitrosamine DBPs in causing cancer by inducing metabolic abnormalities significantly lags behind, and specific mechanisms of toxic effects are not clearly defined. Urgently, further studies exploring this promising area are needed.
摘要：
在最近的SARS-CoV-2爆发期间，加强的卫生措施可能导致氯胺消毒剂向地表水的释放增加，显著促进饮用水中亚硝胺消毒副产物(DBPs)的形成。不幸的是,这些亚硝胺DBPs表现出显著的基因毒性，致癌，和诱变特性，而氯化消毒剂仍在全球实践中。当前的评论提供了对这种情况的宝贵见解，identification,污染状况,暴露极限,以及饮用水中新的不受管制的消毒副产物（亚硝胺DBPs）的毒性。因此,亚硝胺DBPs的浓度远远超过饮用水中的允许限值，长期接触有可能导致代谢紊乱，这是肿瘤发生和发展的关键步骤。重要的是,根据最近的研究，我们总结了亚硝胺DBPs在不同代谢途径中的作用。值得注意的是,亚硝胺DBPs可通过激活鞘脂和多不饱和脂肪酸代谢诱导慢性炎症和引发肿瘤。关于氨基酸和核苷酸代谢，亚硝胺DBPs可以抑制色氨酸（TRP）代谢和从头核苷酸合成。此外，从头核苷酸合成的抑制无法修复由亚硝胺诱导的DNA损伤。此外,由亚硝胺DBPs诱导的乳酸积累可能是肿瘤微环境中通讯的关键信号分子。然而,随着肿瘤代谢组学的发展，了解亚硝胺DBPs在诱导代谢异常致癌中的作用明显滞后，和毒性作用的具体机制没有明确定义。紧急,需要进一步研究探索这个有前途的领域。
