Key Laboratory of Public Health Safety, Ministry of Education, Department of Environmental Health, School of Public Health, Fudan University, 130 Dongan Road Shanghai, 200032, China.
Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
Int J Med Sci. 2017 Aug 18;14(10):961-969. doi: 10.7150/ijms.20121. eCollection 2017.
nitrosamines (NAms), which can arise as byproducts of disinfection agents, are reportedly found in drinking water, and their potential carcinogenicity is a concern; however, little research exists regarding the genotoxicity or carcinogenicity of NAms exposure as a low-dose mixture. The three most common NAms components in China's drinking water are -nitrosodimethylamine (NDMA), -nitrosodiethylamine (NDEA) and -nitrosomethylethylamine (NMEA). Thus, we measured the genotoxic and carcinogenic potential of these compounds and measured the cell cycle and gene expression. The data show that exposure to the NAms-mixture doubled the revertants in the TA98 and TA100 strains and increased the DNA double-strand breaks and the micronuclear frequency in the NIH3T3 cells compared to a single exposure. After long-term NAms mixture exposure, a malignant transformation of NIH3T3 and a significantly increased G2/M distribution were observed. Furthermore, P53, CDK1, P38, CDC25A and CyclinB expressions were down-regulated in the NAms-mixture exposure group; however, P21 and GADD45A genes were up-regulated. Interestingly, the CHK1/CHK2 and CDC25A genes had two responses, depending on the NAms concentrations. Thus, we observed mutagenic, genotoxic and carcinogenic effects after a low-dose NAms-mixture exposure in drinking water, and DNA repair and apoptosis pathways may contribute to these adverse effects.
亚硝胺（NAms）可作为消毒剂的副产物产生，据报道存在于饮用水中，其潜在致癌性令人担忧；然而，关于低剂量混合 NAms 暴露的遗传毒性或致癌性的研究甚少。中国饮用水中三种最常见的 NAms 成分是 -亚硝基二甲胺（NDMA）、-亚硝基二乙胺（NDEA）和 -亚硝基甲基乙胺（NMEA）。因此，我们测量了这些化合物的遗传毒性和致癌潜力，并测量了细胞周期和基因表达。数据表明，与单一暴露相比，NAms 混合物暴露使 TA98 和 TA100 菌株中的回复突变体增加了一倍，并增加了 NIH3T3 细胞中的 DNA 双链断裂和微核频率。长期 NAms 混合物暴露后，观察到 NIH3T3 的恶性转化和显著增加的 G2/M 分布。此外，NAms 混合物暴露组中 P53、CDK1、P38、CDC25A 和 CyclinB 的表达下调；然而，P21 和 GADD45A 基因上调。有趣的是，CHK1/CHK2 和 CDC25A 基因有两种反应，这取决于 NAms 浓度。因此，我们观察到低剂量 NAms 混合物暴露在饮用水中具有致突变、遗传毒性和致癌作用，DNA 修复和细胞凋亡途径可能导致这些不利影响。
