Radiation and Environmental Biophysics

, Volume 47, Issue 1, pp 63–69

Hematopoietic cell renewal systems: mechanisms of coping and failing after chronic exposure to ionizing radiation

Review

Abstract

On the occasion of the first international workshop on systems radiation biology we review the role of cell renewal systems in maintaining the integrity of the mammalian organism after irradiation. First, 11 radiation emergencies characterized by chronic or protracted exposure of the human beings to ionizing irradiation were “revisited”. The data provide evidence to suggest that at a daily exposure of about 10–100 mSv, humans are capable of coping with the excess cell loss for weeks or even many months without hematopoietic organ failure. Below 10 mSv/day, the organisms show some cellular or subcellular indicators of response. At dose rates above 100 mSv/day, a progressive shortening of the life span of the irradiated organism is observed. To elucidate the mechanisms relevant to tolerance or failure, the Megakaryocyte–thrombocyte cell renewal system was investigated. A biomathematical model of this system was developed to simulate the development of thrombocyte concentration as a function of time after onset of chronic radiation exposure. The hematological data were taken from experimental chronic irradiation studies with dogs at the Argonne National Laboratory, USA. The results of thrombocyte response patterns are compatible with the notion of an “excess cell loss” (compared to the steady-state) in all proliferative cell compartments, including the stem cell pool. The “excess cell loss” is a function of the daily irradiation dose rate. Once the stem cell pool is approaching an exhaustion level, a “turbulence region” is reached. Then it takes a very little additional stress for the system to fail. We conclude that in mammalian radiation biology (including radiation medicine), it is important to understand the physiology and pathophysiology of cell renewal systems in order to allow predicting the development of radiation induced lesions.

References

  1. 1.
    Pasteur L (1885) Observations relatives à la note précédente de M. Duclaux. C R Acad Sci Paris 100:68Google Scholar
  2. 2.
    Fliedner TM, Steinbach KH, Hoelzer D (1976) Adaptation of environmental changes: the role of cell-renewal systems. In: Finck ES (ed) The effects of enviornment on cells and tissues. Excerpta Medica, Amsterdam, pp 20–38Google Scholar
  3. 3.
    Stöcker E, Schultze B, Heine W-D, Liebscher H (1972) Growth and regeneration in parenchymatous organs of the rat. Autoradiographic investsigations with 3 H-thymidin. Z f Zellforschung 125:306–331CrossRefGoogle Scholar
  4. 4.
    Fliedner TM, Graessle D, Paulsen C, Reimers K (2002) Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure. Cancer Biother Radiopharm 17(4):405–426CrossRefGoogle Scholar
  5. 5.
    Fliedner TM, Graessle D, Paulsen C, Reimers K, Weiss M (2002) The haematopoietic system: determinants of response to chronic ionizing radiation exposure. In: Fliedner TM, Feinendegen LE, Hopewell JW (eds) Chronic irradiation: tolerance and failure in complex biological systems. British Institute of Radiology, London, pp 247–257Google Scholar
  6. 6.
    Okladnikova ND, K Pesternikova VS, Azizova TV (2002) Deterministic effects of occupational exposure to chronic radiation. In: Fliedner TM, Feinendegen LE, Hopewell JW (eds) Chronic irradiation: tolerance and failure in complex biological systems. British Institute of Radiology, London, pp 26–31Google Scholar
  7. 7.
    Akleyev AV, Kossenko MM, Startsev NV (2002) Techa River population: long-term medical follow-up. In: Fliedner TM, Feinendegen LE, Hopewell JW (eds) Chronic irradiation: tolerance and failure in complex biological systems. British Institute of Radiology, London, pp 32–39Google Scholar
  8. 8.
    Guskova AK, Gusev IA, Okladnikova ND (2002) Russian concepts of chronic radiation disease in man. In: Fliedner TM, Feinendegen LE, Hopewell JW (eds) Chronic irradiation: tolerance and failure in complex biological systems. British Institute of Radiology, London, pp 19–25Google Scholar
  9. 9.
    Enderle GJ, Friedrich K (1995) East German uranium miners (Wismut): exposure, conditions and health consequences. Stem Cells 13(Suppl 1):78–89Google Scholar
  10. 10.
    Feinendegen LE, Graessle D (2002) Energy deposition in tissue during chronic irradiation and the biological consequences. In: Fliedner TM, Feinendegen LE, Hopewell JW (eds) Chronic irradiation: tolerance and failure in complex biological systems. British Institute of Radiology, London, pp 6–14Google Scholar
  11. 11.
    Chang WP, Chan C-C, Wang J-D (1997) 60Co contamination in recycled steel resulting in elevated civilian radiation doses: causes and challenges. Health Phys 73:465–472CrossRefGoogle Scholar
  12. 12.
    Chang WP, Hwang B-F, Wang D, Wang J-D (1997) Cytogenetic effect of chronic low-dose, low-dose-rate γ-radiation in residents of irradiated buildings. Lancet 250:330–333CrossRefGoogle Scholar
  13. 13.
    Baranov AE, Guskova AK, Davtian AA, Sevankaev AV, Lloyd DC, Edwards AA et al (1999) Protracted overexposure to a 137Cs source: II clinical sequelae. Radiat Prot Dosimetry 81:91–100Google Scholar
  14. 14.
    International Atomic Energy Agency (IAEA) (2000) The radiological accident in Lilo. IAEA, Vienna, pp 11–76Google Scholar
  15. 15.
    Martinez RG, Cassab GH, Ganem GG, Guttman EK, Lieberman ML, Vater LB et al (1966) Observations sobre la exposicion accidental de una familia a una fuente de cobalto 60. Revista Medica (Suppl 1):5–60Google Scholar
  16. 16.
    Fliedner TM (1996) Der Strahlenunfall in Estland. In: Reiners C, Messerschmidt O (eds) Die neue Richtlinie physikalische Strahlenschutzkontrolle. Der begrenzte Strahlenunfall. Die Strahlenexposition bei neuen diagnostischen Verfahren. Strahlenschutz in Forschung und Praxis, Vol 38. Gustav Fischer, Stuttgart, pp 94–98Google Scholar
  17. 17.
    Vôsumaa E (2002) The Estonian accident. In: Fliedner TM, Feinendegen LE, Hopewell JW (eds) Chronic irradiation: tolerance and failure in complex biological systems. British Institute of Radiology, London, pp. 71–74Google Scholar
  18. 18.
    Lamerton LF, Pontifex AH, Blackett NM, Adams K (1960) Effects of protracted irradiation on the blood forming organs of the rat. Part I. Continuous exposure. Br J Radiol 33:287–301Google Scholar
  19. 19.
    Lamerton LF (1963) The response of tissues to continuous irradiation. In: Harris RD (ed) Cellular basis and etiology of late somatic effects of ionizing radiation. Academic Press, New York, pp 213–220Google Scholar
  20. 20.
    Lamerton LF (1966) Cell proliferation under continuous irradiation. Radiat Res 27:119CrossRefGoogle Scholar
  21. 21.
    Blackett NM (1967) Erythropoiesis in the rat under continuous gamma-irradiation at 45 rad/day. Br J Haematol 20:915–923Google Scholar
  22. 22.
    Seed TM, Tolle DV, Fritz TE (2002). Haematological responses to chronic irradiation: the past Argonne experience and future AFRRI initiatives. In: Fliedner TM, Feinendegen LE, Hopewell JW (eds) Chronic irradiation: tolerance and failure in complex biological systems. British Institute of Radiology, London, pp 94–102Google Scholar
  23. 23.
    Fritz TE (2002) The influence of dose, dose rate and radiation quality on the effect of protracted whole body irradiation of beagle. In: Fliedner TM, Feinendegen LE, Hopewell JW (eds) Chronic irradiation: tolerance and failure in complex biological systems. British Institute of Radiology, London, pp 103–113Google Scholar
  24. 24.
    Fritz TE, See TM, Tolle DV, Lombard LS (1986) Late effects of protracted whole body irradiation by 60Co gamma rays. In: Thompson RC, Mahaffey IA (eds) Life-span radiation effects studies in animals: what can they tell us? Office of Scientific and Technical Information, United States Department of Energy, Washington, pp 116–141Google Scholar
  25. 25.
    Seed TM, Meyers SM (1993) Chronic radiation-induced alterations in hematopoietic repair during preclinical phases of aplastic anemia and myeloproliferation disease: assessing unscheduled DNA synthesis capacity. Cancer Res 53:4518–4527Google Scholar
  26. 26.
    Graessle DH (2002) Mathematical modelling of the blood platelet renewal system as an approach to analysing the effects of chronic irradiation on haematopoiesis. In: Fliedner TM, Feinendegen LE, Hopewell JW (eds) Chronic irradiation: tolerance and failure in complex biological systems. British Institute of Radiology, London, pp 202–207Google Scholar
  27. 27.
    Hofer EP, Bruecher S, Mehr K, Tibken B (1995) An approach to a biomathematical model of lymphcoytopoiesis. Stem Cells 13(Suppl 1):290–300CrossRefGoogle Scholar
  28. 28.
    Abkowitz JL, Persik MT, Shelton GH, Ott RL, Kiklevich V, Catlin SN et al (1995) Behaviour of hematopoietic stem cells in a large animal. Proc Natl Acad Sci USA 92:2031–2035CrossRefADSGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Radiation Medicine Research Group and WHO Liaison Institute for Radiation Accident Management, Faculty of MedicineUniversity of UlmUlmGermany

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