Fluoride Action Network

home // Researchers // Study Tracker //

Abstract

Fluorides are thought to be a major cause of osteocarcinogenesis, due to their widespread industrial use, ability to accumulate in bone tissue, and genotoxic and probable carcinogenic properties. In vitro experiments investigating the genotoxic potential of fluorides in bone tissue models can provide valuable indirect information on their involvement in osteocarcinogenesis. Here, we investigated whether sodium fluoride (NaF) has the ability to induce DNA damage and chromosomal abnormalities in human osteosarcoma cells after 48 and 72 h of exposure. The cell cultures were treated with NaF in concentrations of 0, 20, 100 and 200 ?g/ml. The level of DNA damage was assessed by the comet assay, and the frequency of chromosomal abnormalities by a micronucleus test. A significant increase in DNA damage indicators was noted in the samples treated with fluoride concentrations of 100 and 200 µg/ml, after 48 and 72 h of exposure. The micronucleus test revealed a dose-dependent increase in cells with micronuclei, nucleoplasmic bridges and nuclear protrusions. Increasing the concentration of NaF led to an increase in the prevalence of cytogenetic indicators after both treatment durations. This demonstrated ability of fluorine to exert genotoxic effects on bone cells indirectly indicates the possible importance of fluoride in the aetiology of osteosarcoma.

*Original abstract online at https://link.springer.com/article/10.1007/s43188-020-00039-0

 

References

  1. Lav KH, Baylink DJ (1998) Molecular mechanism of action of fluoride on bone cells. J Bone Miner Res 13:1660–1667

    Article  Google Scholar

  2. Perumal E, Paul V, Govindarajan V, Panneerselvam L (2013) A brief review on experimental fluorosis. Toxicol Lett 223:236–251

    CAS  Article  Google Scholar

  3. Purohit SD, Gupta RC, Mathur AK, Gupta N, Jeswani ID, Choudhary VK (1999) Experimental pulmonary fluorosis. Indian J Chest Dis Allied Sci 41:27–34

    CAS  PubMed  Google Scholar

  4. Grandjean P, Olsen JH, Jensen OM, Juel K (1992) Cancer incidence and mortality in workers exposed to fluoride. J Natl Cancer Inst 84:1903–1909

    CAS  Article  Google Scholar

  5. Bassin EB, Wypij D, Davis RB, Mittleman MA (2006) Age-specific fluoride exposure in drinking water and osteosarcoma. Cancer Causes Control 17:421–428

    Article  Google Scholar

  6. Ramesh N, Vuayaraghavan AS, Desai BS, Natarajan M, Murthy PB, Pillai KS (2001) Low levels of p53 mutations in Indian patients with osteosarcoma and the correlation with fluoride levels in bone. J Environ Pathol Toxicol Oncol 20:237–243

    CAS  PubMed  Google Scholar

  7. Archer NP, Napier TS, Villanacci JF (2016) Fluoride exposure in public drinking water and childhood and adolescent osteosarcoma in Texas. Cancer Causes Control 27:863–868

    Article  Google Scholar

  8. Gelberg KH, Fitzgerald EF, Synian H, Robert D (1995) Fluoride exposure and childhood osteosarcoma: a case-control study. Am J Public Health 85:1678–1683

    CAS  Article  Google Scholar

  9. Mihashi M, Tsutsui T (1996) Clastogenic activity of sodium fluoride to rat vertebral body-derived cells in culture. Mutat Res 368:7–13

    CAS  Article  Google Scholar

  10. Hirano S, Ando M (1997) Fluoride mediates apoptosis in osteosarcoma UMR 106 and its cytotoxicity depends on the pH. Arch Toxicol 72:52–58

    CAS  Article  Google Scholar

  11. Fenech M (1993) The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations. Mutat Res 285:35–44

    CAS  Article  Google Scholar

  12. Fenech M (2000) The in vitromicronucleus technique. Mutat Res 455:81–95

    CAS  Article  oogle Scholar

  13. Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    CAS  Article  Google Scholar

  14. Das J, Ghosh J, Manna P, Sil PC (2008) Taurine provides antioxidant defense against NaF-induced cytotoxicity in murine hepatocytes. Pathophysiology 15:181–190

    CAS  Article  Google Scholar

  15. Ghosh J, Das J, Manna P, Sil PC (2008) Cytoprotective effect of arjunolic acid in response to sodium fluoride mediated oxidative stress and cell death via necrotic pathway. Toxicol In Vitro 22:1918–1926

    CAS  Article  Google Scholar

  16. Jia L, Zhang Z, Zhai L, Zhang Y, Sun G (2008) DNA damage induced by fluoride in rat kidney cells. Fluoride 41:297–300

    CAS  Google Scholar

  17. Aardema MJ, Gibson DP, LeBoeuf RA (1989) Sodium fluoride-induced chromosome aberrations in different stages of the cell cycle: a proposed mechanism. Mutat Res 223:191–203

    CAS  Article  Google Scholar

  18. Tsutsui T, Suzuki N, Ohmori M (1984) Exchanges, and unscheduled DNA synthesis in cultured Syrian transformation, chromosome aberrations, sister chromatid sodium fluoride-induced morphological and neoplastic hamster embryo cells. Cancer Res 44:938–941

    CAS  PubMed  Google Scholar

  19. He W, Liu A, Bao H, Wang Y, Cao W (1983) Effect of sodium fluoride and fluoroacetamide on sister chromatid exchanges and chromosomal aberrations in cultured Red Muntjac (Muntjacus muntjak) cells. Acta Scient Circumst 3:94–100

    CAS  Google Scholar

  20. Zhang M, Wang A, Xia T, He P (2008) Effects of fluoride on DNA damage, S-phase cell-cycle arrest and the expression of NF-kappaB in primary cultured rat hippocampal neurons. Toxicol Lett 179:1–5

    CAS  Article  Google Scholar

  21. Khalil AM (1995) Chromosome aberrations in cultured in bone marrow cells treated with inorganic fluorides. Mutat Res 343:67–74

    CAS  Article  Google Scholar

  22. Lee TC, Jan KY, Wang TC (1988) Induction of sister chromatid exchanges by arsenite in primary rat tracheal epithelial cells. Bull Inst Zool Acad Sin 27:105–110

    Google Scholar

  23. Tiwari H, Rao MV (2010) Curcumin supplementation protects from genotoxic effects of arsenic and fluoride. Food Chem Toxicol 48:1234–1238

    CAS  Article  Google Scholar

  24. Pant HH, Rao MV (2010) Evaluation of in vitro anti-genotoxic potential of melatonin against arsenic and fluoride in human blood cultures. Ecotoxicol Environ Saf 73:1333–1337

    CAS  Article  Google Scholar

  25. Jachimczak D, Skotarczak B (1978) The effect of fluoride and lead ions on the chromosomes of human leukocytes in vitro. Genet Polon 19:353–357

    Google Scholar

  26. Kleinsasser NH, Weissacher H, Wallner BC et al (2001) Cytotoxicity and genotoxicity of fluorides in human mucosa and lymphocytes. Laryngorhinootologie 80:187–190

    CAS  Article  Google Scholar

  27. Scott D (1985) Cytogenetic effects of sodium fluoride in cultured human fibroblasts. In: 4th international conference on environmental mutagens (Conference proceedings). Stockholm

  28. Hayashi N, Tsutsui T (1993) Cell cycle dependence of cytotoxicity and clastogenicity induced by treatment of synchronized human diploid fibroblasts with sodium fluoride. Mutat Res 290:293–302

    CAS  Article  Google Scholar

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

    CAS  Article  Google Scholar

  30. Wang A, Xia T, Chu Q et al (2004) Effects of fluoride on lipid peroxidation, DNA damage and apoptosis in human embryo hepatocytes. Biomed Environ Sci 17:217–222

    PubMed  Google Scholar

  31. Kishi K, Ishidab T (1993) Clastogenic activity of sodium fluoride in great ape cells. Mutat Res 301:183–188

    CAS  Article  Google Scholar

  32. Jagiello G, Lin JS (1974) Sodium fluoride as potential mutagen in mammalian eggs. Arch Environ Health 29:230–235

    CAS  Article  Google Scholar

  33. Thomson EJ, Kilanowski, Perry PE (1985) The effect of fluoride on chromosome aberration and sister chromatid exchange frequencies in cultured human lymphocytes. Mutat Res 144:89–92

    CAS  Article  Google Scholar

  34. Jothiramajayam M, Sinha S, Ghosh M et al (2014) Sodium fluoride promotes apoptosis by generation of reactive oxygen species in human lymphocytes. J Toxicol Environ Health A 77:1269–1280

    CAS  Article  Google Scholar

  35. Suzuki M, Bandoski C, Bartlett JD (2015) Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling. Free Radic Biol Med 89:369–378

    CAS  Article  Google Scholar

  36. Nguyen Ngoc TD, Son YO, Lim SS, Shi X, Kim JG, Heo JS, Choe Y, Jeon YM, Lee JC (2012) Sodium fluoride induces apoptosis in mouse embryonic stem cells through ROS-dependent and caspase- and JNK-mediated pathways. Toxicol Appl Pharmacol 259:329–337

    CAS  Article  Google Scholar

  37. Dutta M, Rajak P, Khatun S, Roy S (2017) Toxicity assessment of sodium fluoride in Drosophila melanogaster after chronic sub-lethal exposure. Chemosphere 166:255–266

    CAS  Article  Google Scholar

  38. Karube H, Nishitai G, Inageda K, Kurosu H, Matsuoka M (2009) NaF activates MAPKs and induces apoptosis in odontoblast-like cells. J Dent Res 88:461–465

    CAS  Article  Google Scholar

Download references

Acknowledgements

The study was conducted with financial support from the Russian Foundation for Basic Research and the administration of the region of Kemerovo (No 18-44-420012 p_a, agreement with AKO No 8, 28 June 2018), and from a stipend for young scientists from the President of the Russian Federation.

Author information

Affiliations

  1. Department of Genetics, Kemerovo State University, Krasnaya St 6, Kemerovo, Russia, 650000

    V. P. Volobaev, E. E. Kalyuzhnaya, E. A. Schetnikova, A. D. Korotkova, A. A. Naik, S. N. Bach, A. Y. Prosekov & A. V. Larionov

  2. Tomsk State University, Lenin Avenue, 36, Tomsk, Russia, 634050

    E. S. Serdyukova

Corresponding author

Correspondence to V. P. Volobaev.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

*Original abstract online at https://link.springer.com/article/10.1007/s43188-020-00039-0

Print Friendly Version of this pagePrint Get a PDF version of this webpagePDF