The genotoxic potential of mixed nitrosamines in drinking water involves oxidative stress and Nrf2 activation
Andersen, Melvin E.
Crabbe, M. James C.
community health services
Subject Categories::H122 Water Quality Control
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AbstractNitrosamine by-products in drinking water are designated as probable human carcinogens by the IARC, but the health effects of simultaneous exposure to multiple nitrosamines in drinking water remain unknown. Genotoxicity assays were used to assess the effects of both individual and mixed nitrosamines in finished drinking water produced by a large water treatment plant in Shanghai, China. Cytotoxicity and genotoxicity were measured at 1, 10-, 100- and 1000-fold actual concentrations by the Ames test, Comet assay, γ-H2AX assay, and the cytokinesisblock micronuclei assay; oxidative stress and the Nrf2 pathway were also assessed. Nitrosamines detected in drinking water included NDMA (36.45 ng/L), NDPA (44.68 ng/L), and NEMA (37.27 ng/L). Treatment with a mixture of the three nitrosamines at 1000-fold actual drinking-water concentration induced a doubling of revertants in Salmonella typhimurium strain TA100, DNA and chromosome damage in HepG2 cells, while 1–1000-fold concentrations of compounds applied singly lacked these effects. Treatment with 100- and 1000-fold concentrations increased ROS, GSH, and MDA and decreased SOD activity. Thus, nitrosamine mixtures showed greater genotoxic potential than that of the individual compounds. N-Acetylcysteine protected against the nitrosamine-induced chromosome damage, and Nrf2 pathway activation suggested that oxidative stress played pivotal roles in the genotoxic property of the nitrosamine mixtures.
CitationDong L, Jiang Z, Yang L, Hu F, Zheng W, Xue P, Jiang S, Andersen ME, He G, Crabbe MJC, Qu W (2022) 'The genotoxic potential of mixed nitrosamines in drinking water involves oxidative stress and Nrf2 activation', Journal of Hazardous Materials, 426 (March 2022), 128010.
JournalJournal of Hazardous Materials
SponsorsThis project was supported by the National Natural Science Foundation of China (81630088, 81930094, 81273035, & 81325017), Changjiang Scholars Program, Ministry of Education (T2014089), Key Project of National High-tech R&D Program of China Ministry of Science and Technology of the People’s Republic of China (No. 2017YFC1600500 & 2013AA065204), National Key R&D Program of China of and a Non-profit Foundation of National Health Ministry in the 12th Five Year Plan (201002001 & 2012BAJ25B05).
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