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Experientia

, Volume 45, Issue 1, pp 33–41 | Cite as

Cell kinetics and radiation pathology

  • J. Denekamp
  • A. Rojas
Multi-author Review

Conclusion

Radiation pathology is a general term describing the damage that occurs in tissues after irradiation. After the very low doses, received by the normal working population, no major pathology is seen. There is a hazard of cancer induction if DNA damage that has been inflicted in an individual cell is repaired in such a way that the DNA remains intact but rearranged. This radiation carcinogenesis is however a low risk compared with many chemical carcinogens in the environment and in cancer chemotherapy.

The treatment of cancer by radiation is now commonly accepted as one of the most effective forms of treatment. It can kill tumour cells effectively, but the dose that can be given is limited by the normal tissues that are inevitably included in the beam. Cell function is maintained for some time even after very large doses. However normal tissues show a loss of function and structure because the proliferating subcompartment of each tissue is depleted as the radiation injured cells fail to divide and die. The time at which the cell deficit is detected varies from hours in some tissues to months or years in others. It depends upon the normal rate of cell turnover. The apparent sensitivity of each tissue therefore depends upon the time at which the assessment is made. Lung and kidney would appear very resistant at 1–3 months post irradiation, but would seem very radiosensitive at 6–12 months as their latent damage is expressed.

The ultimate expression of radiation pathology is the death of the whole animal as the essential organ function fails. The time of this death is only comprehensible if the time sequence and the proliferation kinetics of the target cells are taken into account. It must be recognised that it is initial damage to the clonogenic cells, not to the differentiated cells per se that is important.

Key words

Cell proliferation kinetic techniques cellular radiosensitivity repair of sublethal injury repopulation radiation pathology tumour cells tissue dysfunction 

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References

  1. 1.
    Aherne, W. A., Camplejohn, R. S., and Wright, N. A., An Introduction to Cell Population Kinetics. Pub. Edward Arnold, London 1977.Google Scholar
  2. 2.
    Alper, T., Fowler, J. F., Morgan, R. L., Vonberg, D. D., Ellis, F., and Oliver, R., The characterisation of the ‘Type C’ survival curve. Br. J. Radiol.35 (1962) 722–723.Google Scholar
  3. 3.
    Begg, A. C., McNally, N. J., Shrieve, D. C., and Kärcher, H., A method to measure the duration of DNA synthesis and the potential doubling time from a single sample. Cytometry6 (1985) 620–626.CrossRefPubMedGoogle Scholar
  4. 4.
    Clausen, O. P. F., Thorud, E., Bjerknes, R., and Elgjo, K., Circadian rhythms in mouse epidermal basal cell proliferation. Variations in compartment size, flux and phase duration. Cell Tiss. Kinet.12 (1979) 319–337.Google Scholar
  5. 5.
    Cullen, B. M., Michalowski, A., and Walker, H. C., Correlation between the radiobiological oxygen constant, K, and the non-protein sulphydryl content of mammalian cells. Int. J. Radiat. Biol.38 (1980) 525–535.Google Scholar
  6. 6.
    Denekamp, J. The cellular proliferation kinetics of animal tumours. Cancer Res.39 (1970) 393–400.Google Scholar
  7. 7.
    Denekamp, J., Changes in the rate of repopulation during multifraction irradiation of mouse skin. Br. J. Radiol.46 (1973) 381–387.PubMedGoogle Scholar
  8. 8.
    Denekamp, J., Cell Kinetics and Cancer Therapy. Ed. W. C. Dewey. C. C. Thomas, Springfield, Illinois 1982.Google Scholar
  9. 9.
    Denekamp, J., Cell kinetics and radiation biology. Int. J. Radiat. Biol.2 (1986) 357–380.Google Scholar
  10. 10.
    Denekamp, J. and Fowler, J. F., Cell proliferation kinetics and radiation therapy, in: Cancer: A Comprehensive Treatise, vol. 6, pp. 101–138 Ed. F. Becker. Plenum, New York/London 1977.Google Scholar
  11. 11.
    Denekamp, J., Stewart, F. A., and Douglas, B. G., Changes in the proliferation rate of mouse epidermis after irradiation: continuous labelling studies. Cell Tiss. Kinet.9 (1976) 19–29.Google Scholar
  12. 12.
    Douglas, B. G., and Fowler, J. F., The effect of multiple small doses of X-rays on skin reactions in the mouse and a basic interpretation. Radiat. Res.66 (1976) 401–426.PubMedGoogle Scholar
  13. 13.
    Elkind, M. M., Han, A., and Volz, K. W., Radiation response of mammalian cells grown in culture. IV. Dose dependence of division delay and post-irradiation growth of surviving and non-surviving Chinese hamster cells. J. natl Canc. Inst.30 (1963) 705–721.Google Scholar
  14. 14.
    Folkman, J., Tumor angiogenesis factor. Cancer Res.34 (1974) 2109–2113.PubMedGoogle Scholar
  15. 15.
    Fowler, J. F., La Ronde — radiation sciences and medical radiology. Radiotherapy Oncology1 (1983) 1–22.Google Scholar
  16. 16.
    Fowler, J. F., Review: Total doses in fractionated radiotherapy —implications of new radiobiological data. Int. J. Radiat. Biol.46 (1984) 103–120.Google Scholar
  17. 17.
    Fowler, J. F., and Denekamp, J., Radiation effects on normal tissues, in: Cancer: A Comprehensive Treatise, vol. 6, pp. 139–176. Ed. F. Becker. Plenum, New York/London 1977.Google Scholar
  18. 18.
    Gratzner, H. G., Monoclonal antibody to 5-bromo- and 5-iodeoxyuridine: A new reagent for detection of DNA replication. Science218 (1982) 474–475.PubMedGoogle Scholar
  19. 19.
    Gray, J. W. (Ed.), Monoclonal antibodies against bromodeoxyuridine. Cytometry6 (1985) 501–662.Google Scholar
  20. 20.
    Gray, L. H., Conger, A. D., Ebert, M., Horney, S., and Scott, O. C. A.: The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br. J. Radiol.26 (1953) 638–648.PubMedGoogle Scholar
  21. 21.
    Howard, A., and Pelc, S. R., Synthesis of deoxyribonucleic acid in normal and irradiated cells and its relation to chromosome breakage. Heredity, Suppl. 6 (1953) 261–273.Google Scholar
  22. 22.
    Lesher, S., and Bauman, J., Cell kinetic studies of the intestinal epithelium: Maintenance of the intestinal epithelium in normal and irradiated animals. Natl Cancer Inst.30 (1969) 185–198.Google Scholar
  23. 23.
    Michalowski, A., Wheldon, T. E., and Kirk, T., Can cell survival parameters be deduced from non-clonogenic assays to normal tissues. Br. J. Cancer49 Suppl. VI (1984) 257–261.Google Scholar
  24. 24.
    Ohara, H., and Terasima, T., Variations of cellular sulphydryl content during cell cycle of HeLa cells and its correlation to cyclic change of X-ray sensitivity. Exp. Cell Res.58 (1969) 182–185.CrossRefPubMedGoogle Scholar
  25. 25.
    Potten, C. S., and Hendry, J. H., Cell Clones: Manual of Mammalian Cell Techniques. Churchill Livingstone, Edinburgh 1985.Google Scholar
  26. 26.
    Quastler, H., and Sherman, F. G., Cell population kinetics in the intestinal epithelium of the mouse. Exp. Cell Res.17 (1959) 420–438.CrossRefPubMedGoogle Scholar
  27. 27.
    Sinclair, W. K., Dependence of radiosensitivity upon cell age, in: Time and Dose Relationships in Radiation Biology as Applied to Radiotherapy, pp. 97–107. BNL Report 50203 (C-57) 1969.Google Scholar
  28. 28.
    Sinclair, W. K., N-ethylmaleimide and the cyclic response to X-rays of synchronous Chinese hamster cells. Radiat. Res.55 (1973) 41–57.PubMedGoogle Scholar
  29. 29.
    Steel, G. G., Cell loss as a factor in the growth rate of human tumours. Eur. J. Cancer3 (1967) 381–387.PubMedGoogle Scholar
  30. 30.
    Steel, G. G., Growth Kinetics of Tumours. Oxford University Press, Oxford 1977.Google Scholar
  31. 31.
    Stevens, G., Joiner, B., and Denekamp, J., Radioprotection by hypoxic breathing. Proc. 6th Conference on Chemical Modifiers of Cancer Treatment, pp. 20–21. Eds E. P. Malaise, G. E. Adams, S. Dische, and M. Guichard. Paris 1988.Google Scholar
  32. 32.
    Stewart, F. A., Soranson, J. A., Alpen, E. L., Williams, M. V. and Denekamp, J., Radiation-induced renal damage: the effects of hyperfraction. Radiat. Res.98 (1984) 407–420.PubMedGoogle Scholar
  33. 33.
    Thames, H. D., Withers, H. R., Peters, L. J., and Fletcher, G. H., Changes in early and late radiation responses with altered dose fractionation: implications for dose-survival relationships. Int. J. Radiat. Oncol. Biol. Phys.8 (1982) 219–226.PubMedGoogle Scholar
  34. 34.
    Wheldon, T. E., Michalowski, A. S., and Kirk, J., The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation. Br. J. Radiol.55 (1982) 759–766.PubMedGoogle Scholar
  35. 35.
    Withers, H. R., Regeneration of intestinal mucosa after irradiation. Cancer28 (1971) 75–81.PubMedGoogle Scholar
  36. 36.
    Withers, H. R., Thames, H. D., and Peters, L. J., Differences in the fractionation response of acutely and late-responding tissues. in: Progress in Radio Oncology II, pp. 287–296.Eds K. H. Karcher, H. D. Kogelnik and G. Reinartz. Raven Press, New York 1982.Google Scholar

Copyright information

© Birkhäuser Verlag 1989

Authors and Affiliations

  • J. Denekamp
    • 1
  • A. Rojas
    • 1
  1. 1.Cancer Research Campaign, Gray LaboratoryMount Vernon HospitalNorthwoodEngland

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