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The genotoxic potential of mixed nitrosamines in drinking water involves oxidative stress and Nrf2 activation

  • Lei Dong
    ,
  • Zhiqiang Jiang
    ,
  • Lili Yang
    ,
  • Fen Hu
    ,
  • Weiwei Zheng
    ,
  • Peng Xue
  • Fudan University
    ,
  • ScitoVation LLC
    ,
  • University of Oxford
Research Output:
Contribution to journal
Article
 Peer-review

Open access

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

Abstract

Nitrosamine 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.

Publication Information

Output type

Research Output:
Contribution to journal
Article
 Peer-review

Original language

English

Article number

128010

Pages from-to (Number of pages)

Pages 128010

Journal (Volume, Issue Number)

Journal of Hazardous Materials (Volume 426, Issue March 2022)

Publication milestones

  • Accepted/In press - 05/12/2021
  • Published - 07/12/2021

Publication status

Published - 07/12/2021

ISSN

0304-3894

Publication IDs

  • handle.net: 10547/625279
  • Scopus: 85121277915

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