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Long-term exposure to low level of fluoride induces apoptosis via p53 pathway in lymphocytes of aluminum smelter workers

Abstract

Long-term occupational exposure to low level of fluoride can induce oxidative stress and apoptosis in many cells, including lymphocyte. However, the underlying mechanism remains unclear. Hence, this study was designed to explore the potential oxidative stress and apoptosis of long-term occupational exposure to low level of fluoride in aluminum smelter workers. A total of 120 aluminum smelter workers were recruited in control, low-, middle-, and high-fluoride exposure groups with 30 workers for each group. The peripheral blood samples were collected, centrifuged, and isolated to obtain serum and lymphocyte suspensions. The air and serum fluoride concentrations were detected by fluoride ion-selective electrode method. The lymphocytic apoptosis rate, DNA damage, oxidative stress, and mRNA levels of p53, Bcl-2, and Bax were assessed by Annexin V/PI staining, comet assay, attenuated total reflectance Fourier transform infrared spectroscopy and real-time polymerase chain reaction, respectively. Results showed that the air and serum fluoride concentrations of fluoride-exposed groups were higher than those of the control group (p < 0.05). Fluoride exposure might induce apoptosis, DNA damage and oxidative stress in a dose-dependent manner in lymphocytes (p < 0.05). The expression levels of p53 and Bax were increased with fluoride exposure in lymphocytes (p < 0.05), whereas the Bcl-2 expression was decreased but not significantly. Taken together, these observations indicate that long-term occupational exposure to low level of fluoride may lead to oxidative stress and induce apoptosis through the p53-dependent pathway in peripheral blood lymphocytes of aluminum smelter workers. Serum fluoride level may be the potential biomarker of fluoride exposure.

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Acknowledgements

The authors would like to thank the volunteers who participated in this study.

Funding

This work was financially sponsored by the Scientific Research Foundation of the Education Department of Guangxi Province (Grant No. 2002316 and KY2015ZD058) and the National Natural Science Foundation (Grant No. 81602888).

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Correspondence to Yueming Jiang or Qijun Wu.

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The authors declare that they have no conflicts of interest.

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Responsible editor: Philippe Garrigues

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Wen, P., Wei, X., Liang, G. et al. Long-term exposure to low level of fluoride induces apoptosis via p53 pathway in lymphocytes of aluminum smelter workers. Environ Sci Pollut Res 26, 2671–2680 (2019). https://doi.org/10.1007/s11356-018-3726-z

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Keywords

  • Fluoride
  • Apoptosis
  • DNA damage
  • Oxidative stress
  • p53-dependent pathway