Skip to main content
SpringerLink
Log in

Genotoxicity Induced by Low Dose and Mixed Exposure to Haloacetaldehydes, an Emerging Class of Drinking Water Disinfection By-products

  • Article
  • Published:
Chemical Research in Chinese Universities Aims and scope

Abstract

Haloacetaldehydes(HALs) are the third largest disinfection by-products(DBPs) class by mass in drinking water. Most of them alone in high doses are more cytotoxic and genotoxic than regulated DBPs. However, the toxic effects of mixed exposure to HALs at environmentally relevant levels are still unknown. Given that genotoxicity is critical for risk assessment, we employed multiple genotoxic tests including the Salmonella typhimurium revertant mutation assay(Ames assay), the single cell gel electrophoresis(SCGE) assay, the cytoplasmic blocking micronucleus(CBMN) assay, and the γ-H2AX assay to investigate the genotoxicity of HALs based on the HALs concentrations and components detected in the finished drinking water of Shanghai, China. The results demonstrated the concentrations of HALs were low, ranging from 0.04 µg/L to 4.47 µg/L, and the total concentration was 10.85 µg/L. Although the mutagenicity of HALs was negative even at 1000-fold concentrations in the real world, mixed exposure to 100 and 1000-fold concentrations HALs resulted in DNA and chromosomal damage in human hepotocyte(HepG2) cells. HALs significantly increased the levels of reactive oxygen species(ROS) and γ-H2AX and activated nuclear factor erythroid-derived factor 2-related factor 2(NRF2) pathway-related protein expressions in HepG2 cells. The antioxidant NAC could ameliorate NRF2 pathway-related protein expression and DNA damage caused by HALs, suggesting that the genotoxicity of mixed exposure to HALs involved cellular oxidative stress and NRF2 pathway activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. King W. D., Marrett L. D., Cancer Causes Control, 1996, 7(6), 596

    CAS  PubMed  Google Scholar 

  2. Srivastav A. L., Patel N., Chaudhary V. K., Environ. Pollut., 2020, 267, 115474

    CAS  PubMed  Google Scholar 

  3. Bove G. E., Rogerson P. A., Vena J. E., Int. J Health Geogr., 2007, 6, 18

    PubMed  PubMed Central  Google Scholar 

  4. Costet N., Villanueva C. M., Jaakkola J. J. K., Kogevinas M., Cantor K. P., King W. D., Lynch C. F., Nieuwenhuijsen M. J., Cordier S., Occup. Environ. Med., 2011, 68(5), 379

    CAS  PubMed  Google Scholar 

  5. Smith R. B., Edwards S. C., Best N., Wright J., Nieuwenhuijsen M. J., Toledano M. B., Environ. Health Perspect, 2016, 124(5), 681

    CAS  PubMed  Google Scholar 

  6. Plewa M. J., Richardson S. D., J. Environ. Sci.(China), 2017, 58, 1

    PubMed  Google Scholar 

  7. Jeong C. H., Postigo C., Richardson S. D., Simmons J. E., Kimura S. Y., Mariñas B. J., Barcelo D., Liang P., Wagner E. D., Plewa M. J., Environ. Sci. Technol., 2015, 49(23), 13749

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Muellner M. G., Wagner E. D., McCalla K., Richardson S. D., Woo Y.-T., Plewa M. J., Environ. Sci. Technol., 2007, 41(2), 645

    CAS  PubMed  Google Scholar 

  9. Plewa M. J., Muellner M. G., Richardson S. D., Fasano F., Buettner K. M., Woo Y.-T., McKague A. B., Wagner E. D., Environ. Sci. Technol., 2008, 42(3), 955

    CAS  PubMed  Google Scholar 

  10. Plewa M. J., Wagner E. D., Jazwierska P., Richardson S. D., Chen P. H., McKague A. B., Environ. Sci. Technol., 2004, 38(1), 62

    CAS  PubMed  Google Scholar 

  11. Wagner E. D., Plewa M. J., J. Environ. Sci.(China), 2017, 58, 64

    CAS  PubMed  Google Scholar 

  12. Krasner S. W., Weinberg H. S., Richardson S. D., Pastor S. J., Chinn R., Sclimenti M. J., Onstad G. D., Thruston A.D., Environ. Sci. Technol., 2006, 40(23), 7175

    CAS  PubMed  Google Scholar 

  13. Koudjonou B., Lebel G. L., Dabeka L., Chemosphere, 2008, 72(6), 875

    CAS  PubMed  Google Scholar 

  14. Sadiq R., Rodriguez M. J., J. Environ. Manage., 2004, 73(1), 1

    PubMed  Google Scholar 

  15. Henson C. M., Emmert G. L., Simone P. S., Chemosphere, 2014, 117, 586

    CAS  PubMed  Google Scholar 

  16. Haworth S., Lawlor T., Mortelmans K., Speck W., Zeiger E., Environ. Mutagen, 1983, 5(Suppl. 1), 1

    PubMed  Google Scholar 

  17. Warr T. J., Parry E. M., Parry J. M., Mutat. Res., 1993, 287(1), 29

    CAS  PubMed  Google Scholar 

  18. Sood C., O’Brien P. J., Biochem. Pharmacol., 1993, 46(9), 1621

    CAS  PubMed  Google Scholar 

  19. Benesic A., Schwerdt G., Mildenberger S., Freudinger R., Gordjani N., Gekle M., Kidney Int., 2005, 68(5), 2029

    CAS  PubMed  Google Scholar 

  20. Pandya G. A., Moriya M., Biochemistry, 1996, 35(35), 11487

    CAS  PubMed  Google Scholar 

  21. Biernat J., Ciesiołka J., Górnicki P., Adamiak R. W., Kryzosiak W. J., Wiewiórowski M., Nucleic Acids Res., 1978, 5(3), 789

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Crebelli R., Conti G., Conti L., Carere A., Mutat. Res., 1984, 138(1), 33

    CAS  PubMed  Google Scholar 

  23. Guengerich F. P., Mason P. S., Stott W. T., Fox T. R., Watanabe P. G., Cancer Res., 1981, 41 (11 Pt 1), 4391

    CAS  PubMed  Google Scholar 

  24. Liviac D., Creus A., Marcos R., Water Res., 2010, 44(8), 2638

    CAS  PubMed  Google Scholar 

  25. Wang Z., Hu H., Hu M., Zhang X., Wang Q., Qiao Y., Liu H., Shen L., Zhou P., Chen Y., Radiat. Environ. Biophys., 2014, 53(2), 283

    CAS  PubMed  Google Scholar 

  26. Niu H., Chang H. C., Cho I. C., Chen C. H., Liu C. S., Chou W. T., Applied Surface Science, 2014, 310, 62

    CAS  Google Scholar 

  27. Dong L., Jiang Z., Yang L., Hu F., Zheng W., Xue P., Jiang S., Andersen M. E., He G., Crabbe M. J. C., Qu W., J. Hazard Mater., 2022, 426, 128010

    CAS  PubMed  Google Scholar 

  28. Wang S., Tian D., Zheng W., Jiang S., Wang X., Andersen M. E., Zheng Y., He G., Qu W., Environ. Sci. Technol., 2013, 47(3), 1678

    CAS  PubMed  Google Scholar 

  29. Standard Examination Methods for Drinking Water-Collection and Preservation of Water Samples, https://openstd.samr.gov.cn/bzgk/gb/newGbInfo?hcno=CA71F3AD8B8B22D908B7ED0FBCF703DF

  30. Serrano M., Silva M., Gallego M., J. Chromatogr. A, 2011, 1218(46), 8295

    CAS  PubMed  Google Scholar 

  31. Koudjonou B. K., LeBel G. L., Chemosphere, 2006, 64(5), 795

    CAS  PubMed  Google Scholar 

  32. Kubo S., Kaji H., Sci. Rep., 2018, 8(1), 13462

    PubMed  PubMed Central  Google Scholar 

  33. Wang S., Zheng W., Liu X., Xue P., Jiang S., Lu D., Zhang Q., He G., Pi J., Andersen M. E., Tan H., Qu W., Environ. Sci. Technol., 2014, 48(22), 13478

    CAS  PubMed  Google Scholar 

  34. Sgro L. A., Simonelli A., Pascarella L., Minutolo P., Guarnieri D., Sannolo N., Netti P., D’Anna A., Environ. Sci. Technol., 2009, 43(7), 2608

    CAS  PubMed  Google Scholar 

  35. Uhl M., Helma C., Knasmüller S., Mutat. Res., 1999, 441(2), 215

    CAS  PubMed  Google Scholar 

  36. Fenech M., Nat. Protoc., 2007, 2(5), 1084

    CAS  PubMed  Google Scholar 

  37. McNamee J. P., Flegal F. N., Greene H. B., Marro L., Wilkins R. C., Radiat. Prot. Dosimetry, 2009, 135(4), 232

    CAS  PubMed  Google Scholar 

  38. Mariotti L. G., Pirovano G., Savage K. I., Ghita M., Ottolenghi A., Prise K. M., Schettino G., PLoS One, 2013, 8(11), e79541

    PubMed  PubMed Central  Google Scholar 

  39. Rothe G., Valet G., J. Leukoc. Biol., 1990, 47(5), 440

    CAS  PubMed  Google Scholar 

  40. Wang S., Zhang H., Zheng W., Wang X., Andersen M. E., Pi J., He G., Qu W., Environ. Sci. Technol., 2013, 47(9), 4768

    CAS  PubMed  Google Scholar 

  41. Zuo Z., Wu T., Lin M., Zhang S., Yan F., Yang Z., Wang Y., Wang C., Environ. Sci. Technol., 2014, 48(9), 5179

    CAS  PubMed  Google Scholar 

  42. Attene-Ramos M. S., Wagner E. D., Plewa M. J., Environ. Sci. Technol., 2010, 44(19), 7206

    CAS  PubMed  Google Scholar 

  43. Kao T.-Y., Chen M.-S., Jou J.-R., Lin C.-P., Tsai T.-H., Ho T.-C., J. Formos. Med. Assoc., 2015, 114(3), 238

    PubMed  Google Scholar 

  44. Postigo C., Jeong C. H., Richardson S. D., Wagner E. D., Plewa M. J., Simmons J. E., Barceló D., Recent Advances in Disinfection By-Products, ACS Symposium Series 1190, American Chemical Society, New York, 2015

  45. Wagner E. D., Osiol J., Mitch W. A., Plewa M. J., Environ. Sci. Technol., 2014, 48(14), 8203

    CAS  PubMed  Google Scholar 

  46. Wilde E. C., Chapman K. E., Stannard L. M., Seager A. L., Brüsehafer K., Shah U.-K., Tonkin J. A., Brown M. R., Verma J. R., Doherty A. T., Johnson G. E., Doak S. H., Jenkins G. J. S., Arch. Toxicol., 2018, 92(2), 935

    CAS  PubMed  Google Scholar 

  47. Caldwell J. C., Mutat. Res., 2012, 751(2), 82

    CAS  PubMed  Google Scholar 

  48. Smith C. J., Perfetti T. A., Berry S. C., Brash D. E., Bus J., Calabrese E., Clemens R. A., Fowle J. R. J., Greim H., MacGregor J. T., Maronpot R., Pressman P., Zeiger E., Hayes A. W., Mutat. Res. Rev. Mutat. Res., 2021, 787, 108363

    CAS  PubMed  Google Scholar 

  49. Barbezan A. B., Martins R., Bueno J. B., Villavicencio A. L. C. H., J. Food Sci., 2017, 82(7), 1518

    CAS  PubMed  Google Scholar 

  50. Madia F., Kirkland D., Morita T., White P., Asturiol D., Corvi R., Mutat. Res. Genet. Toxicol. Environ. Mutagen, 2020, 854/855, 503199

    PubMed  Google Scholar 

  51. Vaca C. E., Fang J. L., Schweda E. K., Chem. Biol. Interact., 1995, 98(1), 51

    CAS  PubMed  Google Scholar 

  52. Krishna G., Hayashi M., Mutat. Res., 2000, 455(1/2), 155

    CAS  PubMed  Google Scholar 

  53. Kalweit S., Utesch D., von der Hude W., Madle S., Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 1999, 439(2), 183

    CAS  Google Scholar 

  54. Thomas P., Umegaki K., Fenech M., Mutagenesis, 2003, 18(2), 187

    CAS  PubMed  Google Scholar 

  55. Bhattacharyya A., Chattopadhyay R., Mitra S., Crowe S. E., Physiol. Rev., 2014, 94(2), 329

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Xu A., Smilenov L. B., He P., Masumura K.-I., Nohmi T., Yu Z., Hei T. K., Environ. Health Perspect, 2007, 115(1), 87

    CAS  PubMed  Google Scholar 

  57. Kinner A., Wu W., Staudt C., Iliakis G., Nucleic Acids Res., 2008, 36(17), 5678

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Yang G., Ibuki Y., Chem. Res. Toxicol., 2018, 31(2), 145

    CAS  PubMed  Google Scholar 

  59. Plewa M. J., Simmons J. E., Richardson S. D., Wagner E. D., Environ. Mol. Mutagen, 2010, 51(8/9), 871

    CAS  PubMed  Google Scholar 

  60. Pals J. A., Ang J. K., Wagner E. D., Plewa M. J., Environ. Sci. Technol., 2011, 45(13), 5791

    CAS  PubMed  Google Scholar 

  61. Palejwala V. A., Simha D., Humayun M. Z., Biochemistry, 1991, 30(36), 8736

    CAS  PubMed  Google Scholar 

  62. Kerins M. J., Ooi A., Antioxid. Redox Signal, 2018, 29(17), 1756

    CAS  PubMed  PubMed Central  Google Scholar 

  63. LoPachin R. M., Gavin T., Chem. Res. Toxicol., 2014, 27(7), 1081

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Beauchamp R. O., Andjelkovich D. A., Kligerman A. D., Morgan K. T., Heck H. D., Crit. Rev. Toxicol., 1985, 14(4), 309

    CAS  PubMed  Google Scholar 

  65. Esterbauer H., Schaur R. J., Zollner H., Free Radic. Biol. Med., 1991, 11(1), 81

    CAS  PubMed  Google Scholar 

  66. Hughes T. B., Miller G. P., Swamidass S. J., Chem. Res. Toxicol., 2015, 28(4), 797

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Lopachin R. M., Gavin T., Decaprio A., Barber D.S., Chem. Res. Toxicol., 2012, 25(2), 239

    CAS  PubMed  Google Scholar 

  68. Pals J. A., Wagner E. D., Plewa M. J., Environ. Sci. Technol., 2016, 50(6), 3215

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Key Project of the National Natural Science Foundation of China(Nos.81630088, 81273035, 81325017) and the Changjiang Scholars Program, Ministry of Education, China(No.T2014089).

Author information

Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of the Public Health Safety, Ministry of Education, Department of Environmental Health, School of Public Health, Fudan University, Shanghai, 200032, P. R. China

    Lili Yang, Wuren Ma, Zhiqiang Jiang, Yu Chen, Meiyue Qiu, Ying Zhou, Weiwei Zheng & Weidong Qu

  2. Wolfson College, Oxford University, Oxford, OX2 6UD, UK

    James C. Crabbe

  3. Institute of Biomedical and Environmental Science & Technology, University of Bedfordshire, Luton, LU1 3JU, UK

    James C. Crabbe

Authors
  1. Lili Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wuren Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhiqiang Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Meiyue Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ying Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. James C. Crabbe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Weiwei Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Weidong Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Weiwei Zheng or Weidong Qu.

Additional information

Conflicts of Interest

The authors declare no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, L., Ma, W., Jiang, Z. et al. Genotoxicity Induced by Low Dose and Mixed Exposure to Haloacetaldehydes, an Emerging Class of Drinking Water Disinfection By-products. Chem. Res. Chin. Univ. 39, 481–491 (2023). https://doi.org/10.1007/s40242-023-3049-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40242-023-3049-6

Keywords

Search

Navigation