Skip to main content

Advertisement

SpringerLink
Log in

Effect of Sodium Fluoride on the Proliferation and Gene Differential Expression in Human RPMI8226 Cells

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Although fluoride is known to reduce the incidence of caries, chronic excessive fluoride exposure can impair human health, even resulting in fluorosis. Now the underlying mechanisms of fluoride-induced toxicity are not fully understood. So, we conducted this study with the purpose of investigating the effect of sodium fluoride (NaF) in human RPMI8226 cells. In this experiment, human RPMI8226 cells were cultured with varied doses of fluoride (10, 20, 40, 80, 160, 320 μM). After 48 h exposure, the change of cell viability was examined by CCK-8 assay, and also the messenger RNA (mRNA) expression of relevant genes was assessed by QRT-PCR. Compared to the control group, fluoride exposure increased the human RPMI8226 cells viability at relatively lower levels (10–160 μM); however, when the concentration reached to 320 μM, the cell proliferation was significantly inhibited (p < 0.05). In addition, the genes mRNA expression, including ANKRD1, CRSP6, KLF2, SBNO2, ZNF649, FANCM, PDGFA, RNF152, CDK10, and CETN2 changed in a concentration-dependent manner and increased with fluoride exposure concentration. The results suggest that overexposure to fluoride (160–320 μM) can induce cytotoxicity and regulate relevant genes expression. Our findings provide novel insights into the mechanisms of action of fluoride-induced toxicity.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Gabuda SP, Gaidash AA, Kozlova SG, Allan NL (2006) Structural forms of fluorides in bone tissue of animals under chronic fluoride intoxication. J Struct Chem 47(2):258–266

    Article  CAS  Google Scholar 

  2. Lianfang W, Jianzhong H (1995) Outline of control practice of endemic fluorosis in China. Soc Sci Med 41(8):1191–1195

    Article  Google Scholar 

  3. Watanabe T, Kondo T, Asanuma S, Sakurai S, Tamura K, Ando M (1997) Endemic fluorosis in southern China: radiological findings. Nihon Igaku Hoshasen Gakkai Zasshi. Nippon Acta Radiol 57(7):425–426

    CAS  PubMed  Google Scholar 

  4. Wei ZD, Wei Y (2002) Fluoridation in China: a clouded future. Fluoride 35(1):1–4

    CAS  Google Scholar 

  5. Ming Z, Aiguo W, Tao X, Ping H (2008) Effects of fluoride on DNA damage, S-phase cell-cycle arrest and the expression of NF-kB in primary cultured rat hippocampal neurons. Toxicol Lett 179:1–5

    Article  Google Scholar 

  6. National Research Council (2006) Fluoride in drinking water: a scientific review of EPA’s standards. The National Academic Press, Washington D.C

    Google Scholar 

  7. Helgeland K, Leirsker J (1976) pH and the cytotoxity of fluoride in an animal cell culture system. Scand J Dent Res 84:37–45

    CAS  PubMed  Google Scholar 

  8. Holland RI (1980) Cytotoxicity of fluoride. Acta Odontol Scand 38:69–79

    Article  CAS  PubMed  Google Scholar 

  9. Barbier O, Arreola ML, Del Razo LM (2010) Molecular mechanisms of fluoride toxicity. Chem-Biol Interact 188(2):319–333

    Article  CAS  PubMed  Google Scholar 

  10. Song JS, Lee HY, Lee E, Hwang HJ, Kim JH (2002) Cytotoxicity and apoptosis induction of sodium fluoride in human promyelocytic leukemia (HL-60) cells. Environ Toxicol Pharmacol 11(2):85–91

    Article  CAS  PubMed  Google Scholar 

  11. Yang T, Zhang Y, Li Y, Hao Y, Zhou M, Dong N, Duan X (2013) High amounts of fluoride induce apoptosis/cell death in matured ameloblast-like LS8 cells by downregulating Bcl-2. Arch Oral Biol 58(9):1165–1173

    Article  CAS  PubMed  Google Scholar 

  12. Zhan XA, Wang M, Xu ZR, Li WF, Li JX (2006) Evaluation of caspase-dependent apoptosis during fluoride-induced liver lesion in pigs. Arch Toxicol 80:74–80

    Article  CAS  PubMed  Google Scholar 

  13. Anarudha CD, Kanno S, Hirano S (2000) Fluoride induces apoptosis by caspase-3 activation in human leukemia HL-60 cells. Arch Toxicol 74:226–230

    Article  Google Scholar 

  14. Hirano S, Ando M (1996) Apoptotic cell death following exposure to fluoride in rat alveolar macrophages. Arch Toxicol 70:249–251

    Article  CAS  PubMed  Google Scholar 

  15. Loweth AC, Williams GT, Scarpello JH, Morgan NG (1996) Heterotrimeric G proteins are implicated in the regulation of apoptosis in pancreatic b-cells. Exp. Cell Res 229:69–76

    Article  CAS  Google Scholar 

  16. Conroy LA, Jenkinson EJ, Owen JT, Michel RJ (1995) Phosphatidylinositol 4,5-bisphosphate hydrolysis accompanies T-cell receptor-induced apoptosis of murine thymocytes within the thymus. Eur J Immunol 25:1828–1835

    Article  CAS  PubMed  Google Scholar 

  17. Liu YJ, Guan ZZ, Gao Q, Pei JJ (2011) Increased level of apoptosis in rat brains and SH-SY5Y cells exposed to excessive fluoride—a mechanism connected with activating JNK phosphorylation. Toxicol Lett 204(2):183–189

    Article  CAS  PubMed  Google Scholar 

  18. Yang S, Wang Z, Farquharson C, Alkasir R, Zahra M, Ren G, Han B (2011) Sodium fluoride induces apoptosis and alters bcl-2 family protein expression in MC3T3-E1 osteoblastic cells. Biochem Biophys Res Commun 410(4):910–915

    Article  CAS  PubMed  Google Scholar 

  19. Slamenˇova´ D, Ga´belova´ A, Ruppova´ K (1992) Cytotoxicity and genotoxicity testing of sodium fluoride on Chinese hamster V79 cells and human EUE cells. Mutat Res 279:109–115

    Article  Google Scholar 

  20. Li P, Xue Y, Zhang W, Teng F, Sun Y, Qu T et al (2013) Sodium fluoride induces apoptosis in odontoblasts via a JNK-dependent mechanism. Toxicology 308:138–145

    Article  CAS  PubMed  Google Scholar 

  21. Lee JH, Jung JY, Jeong YJ, Park JH, Yang KH, Choi NK, Kim SH, Kim WJ (2008) Involvement of both mitochondrial- and death receptor-dependent apoptotic pathways regulated by Bcl-2 family in sodium fluoride-induced apoptosis of the human gingival fibroblasts. Toxicology 243:340–347

    Article  CAS  PubMed  Google Scholar 

  22. Danial NN (2007) BCL-2 family proteins: critical checkpoints of apoptotic cell death. Clin Cancer Res 13(24):7254–7263

    Article  CAS  PubMed  Google Scholar 

  23. Liu XL, Li CC, Liu KJ, Cui CY, Zhang YZ, Liu Y (2012) The influence of fluoride on the expression of inhibitors of Wnt/β-Catenin signaling pathway in rat skin fibroblast cells. Biol Trace Elem Res 148(1):117–121

    Article  CAS  PubMed  Google Scholar 

  24. Duan X, Xu H, Wang Y, Wang H, Li G, Jing L (2014) Expression of core-binding factor α1 and osteocalcin in fluoride-treated fibroblasts and osteoblasts. J Trace Elem Med Biol 28(3):278–283

  25. Yan X, Feng C, Chen Q, Li W, Wang H, Lv L, Wang J et al (2009) Effects of sodium fluoride treatment in vitro on cell proliferation, apoptosis and caspase-3 and caspase-9 mRNA expression by neonatal rat osteoblasts. Arch Toxicol 83(5):451–458

    Article  CAS  PubMed  Google Scholar 

  26. Dangel NJ, Knoll A, Puchta H (2014) MHF1 plays Fanconi anaemia complementation group M protein (FANCM)-dependent and FANCM-independent roles in DNA repair and homologous recombination in plants. Plant J 78(5):822–833

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research presented here was supported by the MEP-PRC Project 2012ZX07101-002&20110 9025. The authors are extremely grateful to the staff at the Department of Environment and Health and the Minzu University of China for their health statistics technical assistance. The findings and conclusions in this report are those of the authors.

Conflict of Interest

The authors declare that there is no conflict of interest.

Author information

Authors and Affiliations

  1. State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Chaoyang District, Beijing, 100012, China

    Hong He, Hongmei Wang, Congli Ma, Han Zhang & Zhou Zhou

  2. College of Life and Environmental Science, Minzu University of China, Haidian District, Beijing, 100081, China

    Hong He, Yuguo Jiao & Congli Ma

Authors
  1. Hong He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongmei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuguo Jiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Congli Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Han Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhou Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hongmei Wang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, H., Wang, H., Jiao, Y. et al. Effect of Sodium Fluoride on the Proliferation and Gene Differential Expression in Human RPMI8226 Cells. Biol Trace Elem Res 167, 11–17 (2015). https://doi.org/10.1007/s12011-015-0271-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-015-0271-1

Keywords

Search

Navigation