Journal of Endocrinological Investigation

, Volume 19, Issue 2, pp 119–126 | Cite as

Cytotoxic effects of iodide on thyroid cells: Difference between rat thyroid FRTL-5 cell and primary dog thyrocyte responsiveness

  • J. Golstein
  • J. E. Dumont


In order to investigate whether the cytotoxic effect of iodide observed in the thyroid gland represented an apoptotic phenomenon, in vitro experiments were performed using the FRTL-5 thyroid cell line and dog thyrocytes in primary culture. These cells were exposed to iodide under various incubation conditions. Apoptosis was assessed through the analysis of DNA breakdown, i.e. the electrophoresis of internucleosomal DNA fragments generating a typical “ladder” and quantification of prelabelled DNA cleavage products. The FRTL-5 cells appeared to be sensitive only to high doses of iodide, far in excess of physiological levels. They exhibited the different characteristics of two different cell death phenomena: apoptosis and necrosis. The toxicity of iodide appeared to be partially relieved by anti-thyroid agents. This effect constitutes an additional example of the general paradigm of iodide action through oxidized intermediates. In contrast dog thyrocytes in primary culture did not appear to be sensitive to iodide under similar incubation conditions; species differences and/or types of culture could account for these discrepant effects.


Iodide cytotoxicity FRTL-5 thyroid cells dog thyrocytes apoptosis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kerr J.F.R., Wyllie A.H., Currie A.R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26: 239, 1972.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Wyllie A.H., Kerr J.F.R., Currie A.R. Cell death: the significance of apoptosis. Int. Rev. Cytology 68: 251, 1980.CrossRefGoogle Scholar
  3. 3.
    Collins M.K.L., Lopez Rivas A. The control of apoptosis in mammalian cells. TIPS 18: 307, 1993.Google Scholar
  4. 4.
    Dremier S., Golstein J., Mosselmans R., Dumont J.E., Galand P., Robaye B. Apoptosis in dog thyroid cells. Biochem. Biophys. Res. Commun. 200: 52, 1994.PubMedCrossRefGoogle Scholar
  5. 5.
    Mahmoud I., Colin I., Many M.C., Denef J.F. Direct toxic effect of iodide in excess on iodine-deficient thyroid glands: epithelial necrosis and inflammation associated lipofusion accumulation. Exp. Mol. Pathol. 44: 259, 1986.PubMedCrossRefGoogle Scholar
  6. 6.
    Denef J.F, Ovaert C., Many M.C. La goitrogenèse expérimentale. Ann. Endocrinol. (Paris) 50: 1, 1989.Google Scholar
  7. 7.
    Rognoni J.B., Penel C., Golstein J., Galand P., Dumont J.E. Régulation possible de la croissance du tissu thyroïdien par l’iodure plasmatique. C.R. Acad. Sci. Paris 13: 635, 1985.Google Scholar
  8. 8.
    Sherwin J.R., Tong W. Thyroidal autoregulation. Iodide-induced suppression of thyrotropin-stimulated cyclic AMP production and iodinating activity in thyroid cells. Biochim. Biophys. Acta 404: 30, 1975.Google Scholar
  9. 9.
    Rapoport B., West M.N., Ingbar S.H. On the mechanism of inhibition by iodine of the thyroid adenylate cyclase response to thyrotropin hormone. Endocrinology 99: 11, 1976.PubMedCrossRefGoogle Scholar
  10. 10.
    Takasu N., Handa Y., Kawaoi A., Shimizu Y., Yamada T. Effects of iodide on thyroid follicle structure and electrophysiological potentials in cultured thyroid cells. Endocrinology 117: 71, 1985.PubMedCrossRefGoogle Scholar
  11. 11.
    Cowin A.J., Bidey S.P. Transforming growth factor ß1 synthesis in human thyroid follicular cells: differential effects of iodide and plasminogen on the production of latent and active peptide forms. J.Endocrinol. 141: 183, 1994.PubMedCrossRefGoogle Scholar
  12. 12.
    Oberhammer F., Bursch W., Parzefall W., Breit P., Erbert E., Stadler M., Schulte-Hermann R. Effect of transforming growth factor ß on cell death of cultured rat hepatocytes. Cancer Res. 51: 2478, 1991.PubMedGoogle Scholar
  13. 13.
    Ambesi-Impiombato F.S., Picone R., Tramontano D. In: Growth of cells in hormonally defined media. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1982, p. 483.Google Scholar
  14. 14.
    Roger P.P., Hotinsky A., Moreau C., Dumont J.E. Stimulation by thyrotropin, cholera toxin and dibutyryl cyclic AMP of the multiplication of differentiated thyroid cells in vitro. Mol. Cell. Endocrinol. 26: 165, 1982.PubMedCrossRefGoogle Scholar
  15. 15.
    Roger P.P., Servais P., Dumont J.E. Induction of DNA synthesis in dog thyrocytes in primary culture: synergistic effects of thyrotropin and cyclic AMP with epidermal growth factors and insulin. J. Cell. Physiol. 130: 58, 1987.PubMedCrossRefGoogle Scholar
  16. 16.
    Robaye B., Dumont J.E. Phospholipase A2 activity is not involved in the tumor necrosis factor — triggered apoptotic DNA fragmentation in bovine endothelial cells. Biochem. Biophys. Res. Commun. 188: 1312, 1992.PubMedCrossRefGoogle Scholar
  17. 17.
    Sambrook J., Fritish E.F., Maniatis T. Molecular Cloning: a laboratory manual, 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1989.Google Scholar
  18. 18.
    McConkey D.J., Orrenius S., Jondal M. Agents that elevate cAMP stimulate DNA fragmentation in thymocytes. J. Immunol. 145: 1227, 1990.PubMedGoogle Scholar
  19. 19.
    Compton M.M. A biochemical hallmark of apoptosis: internucleosomal degradation of the genome. Cancer Metastasis Rev. 11: 105, 1992.PubMedCrossRefGoogle Scholar
  20. 20.
    Taniguchi S., Yoshida A., Mashiba H. Direct effect of methimazole on rat thyroidal cell growth induced by thyrotropin and insulin-like growth factor I. Endocrinology 124: 2046, 1989.PubMedCrossRefGoogle Scholar
  21. 21.
    Beere H.M., Tomlinson S., Bidey S.P. Iodide autoregulation of functional and morphological differentiation events in the FRTL5 rat thyroid cell strain. J. Endocrinol. 124: 19, 1990.PubMedCrossRefGoogle Scholar
  22. 22.
    Smerdely P., Pitsiavas V., Boyages S.C. Evidence that the inhibitory effects of iodide on thyroid cell proliferation are due to arrest of the cell cycle at G0G1 and G2M phases. Endocrinology 133: 2881, 1993.PubMedGoogle Scholar
  23. 23.
    Darzynkiewicz Z., Bruno S., Del Bino G., Gorczyca W., Hotz M.A., Lassota P., Traganos F. Features of apoptotic cells measured by flow cytometry. Cytometry 13: 795, 1992.PubMedCrossRefGoogle Scholar
  24. 24.
    Katoh R., Muramatsu A., Kawaoi A., Komiyama A., Suzuki K., Hemmi A., Katayama S. Alteration of the basement membrane in human thyroid diseases: an immunohistochemical study of type IV collagen, lamicin and heparan sulfate proteoglycan. Virchows Archiv. A Pathol. Anat. Histopathol. 423: 417, 1993.CrossRefGoogle Scholar
  25. 25.
    Eggo M.C., Mak W.W., Bachrach L.K., Errick J.E., Burrow G.N. Cultured thyroids — Is immortality the answer? Endocrine Res. Ther. 2: 201, 1985.Google Scholar
  26. 26.
    Roger P.P., Dumont J.E. Factors controlling proliferation and differentiation of canine thyroid cells cultured in reduced serum conditions: effects of thyrotropin, cyclic AMP and growth factors. Mol. Cell. Endocrinol. 36: 79, 1984.PubMedCrossRefGoogle Scholar
  27. 27.
    Pereira A., Braekman J.C., Dumont J.E., Boeynaems J.M. Identification of a major iodolipid from the horse thyroid gland as 2-iodohexadecanal. J. Biol. Chem. 265: 17018, 1990.PubMedGoogle Scholar
  28. 28.
    Van Sande J., Grenier G., Willems C., Dumont J.E. Inhibition by iodide of the activation of the thyroid cyclic 3′,5′-AMP system. Endocrinology 96: 781, 1975.PubMedCrossRefGoogle Scholar
  29. 29.
    Dumont J.E. The action of thyrotropin on thyroid metabolism. Vitamins and Hormones. Academic Press (NY and London) 29: 287, 1971.CrossRefGoogle Scholar
  30. 30.
    Halliwell B., Gutteridge J.M.C. The antioxidants of human extracellular fluids. Arch. Biochem. Biophysics 280: 1, 1990.CrossRefGoogle Scholar
  31. 31.
    Rodesch F., Jortay A., Dumont J.E. Two different iodinating systems in isolated thyroid cells. Experientia 24: 268, 1968.PubMedCrossRefGoogle Scholar
  32. 32.
    Pekary A.E., Berg L., Wang J., Lee P., Dubinett S.M., Hershman J.M. TNF-α, TSH, and aging regulate TGF-ß synthesis and secretion in FRTL-5 rat thyroid cells. Am. J. Physiol. 268: R808, 1995.PubMedGoogle Scholar
  33. 33.
    Mandel P. ADP-ribosylation: approach to molecular basis of aging. Adv. Exp. Med. Biol. 296: 329, 1991.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1996

Authors and Affiliations

  • J. Golstein
    • 1
  • J. E. Dumont
    • 1
  1. 1.Faculty of MedicineI.R.I.B.H.N. - ULBBrusselsBelgium

Personalised recommendations