Int J Med Sci 2017; 14(10):961-969. doi:10.7150/ijms.20121
Genotoxicity of a Low-Dose Nitrosamine Mixture as Drinking Water Disinfection Byproducts in NIH3T3 Cells
1. 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;
2. Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China;
3. Department of Biostatistics, School of Public Health, Fudan University, Shanghai, 200032, China.
Wang Hy, Qin M, Dong L, Lv Jy, Wang X. Genotoxicity of a Low-Dose Nitrosamine Mixture as Drinking Water Disinfection Byproducts in NIH3T3 Cells. Int J Med Sci 2017; 14(10):961-969. doi:10.7150/ijms.20121. Available from http://www.medsci.org/v14p0961.htm
N-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 N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) and N-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 S. typhimurium 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.
Keywords: Nitrosamines, disinfection byproducts, mixed exposure, genotoxicity, mutagenicity, transformation, DNA repair.