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Pharmacy World and Science

, Volume 20, Issue 5, pp 214–218 | Cite as

Cytogenetic effects on lymphocytes in osteoporotic patients on long-term fluoride therapy

  • Paul Asten
  • Firouz Darroudi
  • Adaqapalam T. Natarajan
  • Ido J. Terpstra
  • Symen A. Duursma
Article

Abstract

The genotoxicity of fluoride in vivo in seven patients with osteoporosis was cytogenetically investigated. The patients were treated with fluoride‐containing formulations (disodium monofluorophosphate and sodium fluoride) for a period of 15 months up to 49 months. Fluoride intake ranged from 22.6‐33.9 mg F-/day and serum fluoride concentrations were between 0.1 mg F-/l and 0.2 mg F-/l. Peripheral blood lymphocytes of these patients were cultured in vitro and examined for chromosomal aberrations, micronuclei in cytokinesis‐blocked binucleated lymphocytes as well as cell cycle progression. When a comparison was made between patients' group and a matched control group, it was found that fluoride at the tested concentrations had no detectable genotoxic potential in human lymphocytes in vivo.

Cytogenetic effects Lymphocytes Disodium monofluorophosphate Genotoxicity Osteoporosis Patient study Sodium fluoride 

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References

  1. 1.
    Philips S, Fox N, Jacobs J, Wright WE. The direct medical costs of osteoporosis for American women aged 45 and older. Bone 1988;9: 271–9.Google Scholar
  2. 2.
    Dempster W, Lindsay R. Pathogenesis of osteoporosis. Lancet 1993;341: 797–801.Google Scholar
  3. 3.
    Duursma SA, Raymakers JA, Scheven BAA, Jansen PAF. Osteoporosis reviews in clinical gerontology 1993;3: 135–46.Google Scholar
  4. 4.
    Riggs BL. Fluoride revisited. Research and Clinical Forums 1993;15(1): 36–9.Google Scholar
  5. 5.
    Li Y, Dunipace AJ, Stooky GK. Genotoxic effects of fluoride: a controversial issue. Mutat Res 1988;195: 127–36.Google Scholar
  6. 6.
    Baylink DJ. Serum fluoride levels. In Primer on metabolic bone diseases and disorders of mineral metabolism. 1st ed. 170–1. Kelseyville, CA: American Society for Bone and Mineral Research, California, 1990.Google Scholar
  7. 7.
    Albanese R. Sodium fluoride and chromosome damage (in vitro human lymphocytes and in vivo micronucleus assays). Mutagenesis 1987;6: 497–9.Google Scholar
  8. 8.
    Kishi K, Tonomura A. Cytogenetic effects of sodium fluoride. Mutat Res 1984;130: 367(abstract).Google Scholar
  9. 9.
    Scott D, Roberts SA. Extrapolation from in vitro tests to human risk. Experience with sodium fluoride clastogenicity. Mutat Res 1987;189: 47–58.Google Scholar
  10. 10.
    Kaminsky LS, Mahoney MC, Leach J, Melius J, Miller MJ. Fluoride: benefits and risks of exposure. Crit Rev Oral Biol Med 1990;1(4): 268–81.Google Scholar
  11. 11.
    Zeiger E, Shelby MD, Witt KI. Genetic toxicity of fluoride. Environ Mol Mutagen 1993;21(4): 309–18.Google Scholar
  12. 12.
    Perry P, Wolff S. New Giemsa method for the differential staining of sister chromatids. Nature (London) 1974;251: 156–68.Google Scholar
  13. 13.
    Glerum JH, van Dijk A, Klein SW. A new and improved gas chromatographic method for the determination of fluoride in plasma and feaces. Pharm Weekbl [Sci] 1984;6: 75–9.Google Scholar
  14. 14.
    Smith GE. Is fluoride a mutagen? Sci Tot Environ 1988;68: 79–96.Google Scholar
  15. 15.
    Thomson EJ, Kolanowski FM, Perry PE. The effect of fluoride on chromosome aberration and sister-chromatid exchange frequencies in cultured human lymphocytes. Mutation Res 1985;144: 89–92.Google Scholar
  16. 16.
    Carrano AV, Natarajan AT. Considerations for population monitoring using cytogenic techniques. ICPEMC Publication no14. Mutat Res 1988;204: 379–407.Google Scholar
  17. 17.
    Evans HJ, O'Riordan ML. Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests. Mutat Res 1975;31: 135–48.Google Scholar
  18. 18.
    Rich C, Feist E. The actions of fluoride on bone. In Vischer TL, ed. Fluoride in medicine. Bern: Huber, 1970: 70–87.Google Scholar
  19. 19.
    Duffery PH, Tratbar HC, Jarkowski TL. Giant cells in bone marrow of patients on high dose fluoride treatment. Ann Intern Med 1971;76: 745–7.Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Paul Asten
    • 1
  • Firouz Darroudi
    • 2
    • 3
  • Adaqapalam T. Natarajan
    • 2
    • 3
  • Ido J. Terpstra
    • 4
  • Symen A. Duursma
    • 5
  1. 1.Department of Hospital PharmacyUtrecht University HospitalUtrechtThe Netherlands
  2. 2.MGC, Department of Radiation Genetics and Chemical MutagenesisLeiden UniversityLeidenThe Netherlands
  3. 3.J.A. Cohen Institute of Radiopathology and Radiation ProtectionInteruniversity InstituteLeidenThe Netherlands
  4. 4.Yamanouchi Europe B.V.LeiderdorpThe Netherlands
  5. 5.Department of GeriatricsUtrecht University HospitalUtrechtThe Netherlands

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