Tight Junctional Changes Upon Microwave and X-Ray Irradiation


Tight junctions (zonulae occludentes, ZO) are cellularly regulated dynamic structures sensitive to environmental stress agents including ionizing radiation. Radiation induced pathological alterations of the small intestine (gastrointestinal radiation syndrome) are related to altered ZO-mediated paracellular transport. We carried out a quantitative morphological evaluation of the murine jejunal epithelial tight junctional structure in freeze fracture replicas as changed upon whole body X-ray irradiation and low energy microwave exposition. X-ray treatment (4 Gy, 1, 24 h) brought about a partial dearrangement of the ZO strand network which regenerated only partially by 24 h. This observation is in line with data on paracellular permeability increases and ZO-bound calcium drop caused by X-ray irradiation. On the other hand, microwave treatment (16 Hz-modulated 2.45 GHz wave, 1 mW/cm2 power density, 1 h exposition, samples at 1 and 3 h after exposition) did not cause dearrangement but, rather an increase in the integration of thight junctional structure, which is in agreement with an increase in cytochemically detectable ZO-bound calcium.


  1. 1.

    Allgood, J. W., Langberg, C. W., Sung, C. C., Hauer-Jensen, M. (1996) Timing of concomitant boost irradiation affects incidence and severity of intestinal complications. Internatl. J. Radiat. Oncol. Biol. Phys. 34, 381–387.

    CAS  Article  Google Scholar 

  2. 2.

    Anderson, J. M., Vanitallie, C. M. (1995) Tight junctions and the molecular basis for regulation of paracellular permeability. Amer. J. Physiol. 32, G467–G475.

    Google Scholar 

  3. 3.

    Ballard, S. T., Hunter, J. H., Taylor, A. E. (1995) Regulation of tight-junction permeability during nutrient absorption across the intestinal epithelium. Annu. Rev. Nutr. 15, 35–55.

    CAS  Article  Google Scholar 

  4. 4.

    Björk, E., Isaksson, U., Edman, P., Artursson, P. (1995) Starch microspheres induce pulsatile delivery of drugs and peptides across the epithelial barrier by reversible separation of the tight junctions. J. Drug targeting 2, 501–507.

    Article  Google Scholar 

  5. 5.

    Boulenc, X., Roques, C., Joyeux, H., Berger, Y., Fabre, G. (1995) Bisphosphonates increase tight junction permeability in the human intestinal epithelial (Caco-2) model. Internatl. J. Pharmaceut. 123, 13–24.

    CAS  Article  Google Scholar 

  6. 6.

    Brayden, D. J., Creed, E., Meehan, E., O’Malley, K. E. (1996) Passive transepithelial diltiazem absorption across intestinal tissue leading to tight junction openings. J. Controlled Release 38, 193–203.

    CAS  Article  Google Scholar 

  7. 7.

    Buell, M. G., Harding, R. K. (1989) Proinflammatory effects of local abdominal irradiation on rat gastrointestinal tract. Dig Dis. Sci. 34, 390–399.

    CAS  Article  Google Scholar 

  8. 8.

    Busch, D. B. (1990) Pathology of the radiation-damaged bowel. In: Galland, R. B. and Spencer, J. (eds) Radiation enteritis. London, Edward Arnold, pp. 66–87.

    Google Scholar 

  9. 9.

    Claude, P., Goodenough, D. A. (1973) Fracture faces of zonule occludents from “tight” and “leaky” epithelia J. Cell Biol. 58, 390–400.

    CAS  Article  Google Scholar 

  10. 10.

    Easter, D. W., Wade, J. B., Boyer, J. L. (1983) Structural integrity of hepatocyte tight junctions. J. Cell Biol. 96, 745–749.

    CAS  Article  Google Scholar 

  11. 11.

    Fasano, A., Fiorenti, C., Donelli, G., Uzzau, S., Kaper, J. B., Margaretten, K., Ding, X., Guandalini, S., Comstock, L., Goldblum, S. E. (1995) Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J. Clin. Investigation 96, 710–720.

    CAS  Article  Google Scholar 

  12. 12.

    Hauser-Jensen, M. (1990) Late radiation injury of the small intestine. Clinical, pathophysiologic and radiobiologic aspects. Acta Oncologica 29, 401–415.

    Article  Google Scholar 

  13. 13.

    Hochman, J., Artusson, P. (1994) Mechanisms of absorption enhancement and tight junction regulation. J. Controlled Release 29, 253–267.

    CAS  Article  Google Scholar 

  14. 14.

    Hirsch, M., Noske, W. (1993) The tight junction, structure and function. Micron 24, 325–352.

    CAS  Article  Google Scholar 

  15. 15.

    Langberg, C. W., Hauer-Jensen, M. (1996) Influence of fraction size on the development of late radiation enteropathy. An experimental study in the rat. Acta Oncologica 35, 89–94.

    CAS  Article  Google Scholar 

  16. 16.

    Leach, L., Firth, J. A. (1995) Advances in understanding permeability in fetal capillaries of the human placenta: a review of the organization of the endothelial paracellular clefts and their junctional complexes. Reprod. Fertil. Dev 7, 1451–1456.

    CAS  Article  Google Scholar 

  17. 17.

    Madara, J. L. (1987) Intestinal absorptive cell tight junctions are linked to cytoskeleton. Amer J. Physiol. 253, C171–C175.

    CAS  Article  Google Scholar 

  18. 18.

    Madara, J. L., Barenberg, D., Carlson, S. (1983) Effects of cytochalasin D on occluding junctions of intestinal absorptive cells; further evidence that the cytoskeleton may influence paracellular permeability and junctional charge selectivity. J. Cell Biol. 102, 2125–2136.

    Article  Google Scholar 

  19. 19.

    Madara, J. L., Carlson, S., Anderson, J. M. (1993) ZO-1 maintains its spatial distribution but dissociates from junctional fibrils during tight junction regulation. Am. J. Physiol. 264, C1096–C1101.

    CAS  Article  Google Scholar 

  20. 20.

    Madara, J. L., Moore, R., Carlson, S. (1987) Alteration of intestinal tight junction structure and permeability by cytoskeletal contraction. Am. J. Physiol. 253, C854–C861.

    CAS  Article  Google Scholar 

  21. 21.

    Madara, J. L., Pappenheimer, J. R. (1987) Structural basis for physiological regulation of paracellular pathways in intestinal epithelia. J. Membr. Biol. 100, 149–164.

    CAS  Article  Google Scholar 

  22. 22.

    Nusrat, A., Parkos, C. A., Verkade, P., Foley, C. S., Liang, T. W., Innis-Whitehouse, W., Eastburn, K. K., Madara, J. L. (2000) Tight junctions are membrane microdomains. J. Cell Science 113, 1771–1781.

    CAS  PubMed  Google Scholar 

  23. 23.

    Otchy, D. P., Nelson, H. (1993) Radiation injuries of the colon and rectum. Surgical Clin. North Amer 73, 1017–1035.

    CAS  Article  Google Scholar 

  24. 24.

    Porvaznik, M. (1979) Tight junction disruption and recovery after sublethal γ irradiation. Radiation Research 78, 233–250.

    CAS  Article  Google Scholar 

  25. 25.

    Potten, C. S. (1995) Structure, function and proliferative organisation of mammalian gut. In: Potten, C. S and Hendry, J. H. (eds) Radiation and Gut. Elsevier.

    Google Scholar 

  26. 26.

    Potten, C. S., Hendry, J. H., Moore, J. V., Chwalinski, S. (1983) Cytotoxic effects in gastro-intestinal epithelium (as exemplified by small intestine). In: Potten, C. S and Hendry, J. H. (eds) Cytotoxic Insult to Tissue. Effects on Cell Lineages. Churchill Livingstone, Edinburgh, London, Melbourne and New York, pp. 105–152.

    Google Scholar 

  27. 27.

    Potten, C. S., Merritt, A., Hickman, J., Hall, P., Faranda, A. (1994) Characterization of radiation-induced apoptosis in the small intestine and its biological implications. Int. J. Radiat. Biol. 65, 71–78.

    CAS  Article  Google Scholar 

  28. 28.

    Quastler, H. (1956) The nature of intestinal radiation death. Radiat. Res. 4, 303–320.

    CAS  Article  Google Scholar 

  29. 29.

    Quastler, H., Hampton, J. C. (1962) Effects of ionizing radiation on the fine structure and function of the intestinal epithelium of the mouse. I. Villus epithelium. Radiat. Res. 17, 914–931.

    CAS  Article  Google Scholar 

  30. 30.

    Somosy, Z. (2000) Radiation response of cell organelles. Micron 31, 165–181.

    CAS  Article  Google Scholar 

  31. 31.

    Somosy, Z., Horváth, Gy., Telbisz, Á., Réz, G., Pálfia, Zs. (2000) Morphological aspects of radiation response of small intestine. Micron 32 (in press).

  32. 32.

    Somosy, Z., Kovács, J., Siklós, L., Köteles, G. J. (1993) Morphological and histochemical changes in intercellular junctional complexes in epithelial cells of mouse small intestine upon X-irradiation: changes of ruthenium red permeability and calcium content. Scanning Microscopy 7, 961–971.

    CAS  PubMed  Google Scholar 

  33. 33.

    Somosy, Z., Sass, M., Bognár, G., Kovács, J., Köteles, G. J. (1995) X-irradiation-induced disorganization of cytoskeletal filaments and cell contacts in HT-29 cells. Scanning Microscopy 9, 763–772.

    CAS  PubMed  Google Scholar 

  34. 34.

    Somosy, Z., Thuróczy, G., Köteles, G. J., Kovács, J. (1994) Effects of modulated microwave and X-ray irradiation on the activity and distribution of Ca2+-ATPase in small intestine epithelial cells. Scanning Microscopy 8, 613–620.

    CAS  PubMed  Google Scholar 

  35. 35.

    Stein, J., Kottra, G. (1997) Intestinal intracellular tight junctions. I. Structure and molecular mechanisms of regulation. Gastroenterology 35, 205–220.

    CAS  Google Scholar 

  36. 36.

    Stevenson, B. R., Anderson, J. M., Godenough, D. A., Mooseker, M. S. (1988) Tight junction structure and ZO-1 in two strains of Madin-Darby canine kidney cells which differ in transepithelial resistance. J. Cell Biol. 107, 2401–2408.

    CAS  Article  Google Scholar 

  37. 37.

    Wolburg, H., Neuhaus, J., Kniesel, U., Krauss, B., Schmid, E.-M., Öcalan, M., Farell, C., Risau, W. (1994) Modulation of tight junction structure in blood-brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes. J. Cell Sci. 107, 1347–1357.

    CAS  PubMed  Google Scholar 

  38. 38.

    Young, R. W. (1987) Acute radiation syndrome. In: Conklin, J. J., Walker, R. I. (eds) Military Radiobiology. Academic Press Inc. pp. 165–190.

    Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Z. Pálfia.

Additional information

Dedicated to Professor János Kovács on the occasion of his 70th birthday

Rights and permissions

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Pálfia, Z., Somosy, Z. & Réz, G. Tight Junctional Changes Upon Microwave and X-Ray Irradiation. BIOLOGIA FUTURA 52, 411–416 (2001). https://doi.org/10.1556/ABiol.52.2001.4.6

Download citation


  • Tight junction
  • zonula occludens
  • freeze-fracture
  • X-ray
  • microwave