Skip to main content
SpringerLink
Log in

Rescue of Lethally Irradiated Animals

Therapeutic Use of rhG-CSF and rhGM-CSF in Preclinical Models of Radiation-Induced Marrow Aplasia

  • Chapter
Treatment of Radiation Injuries

Abstract

Three recent radiation accidents—the reactor explosion in Chernobyl, U.S.S.R.,1 the external and internal cesium-137 exposure in Goiânia, Brazil,2 and the cobalt-60 exposure of three technicians in El Salvador, San Salvador—exemplify the usual conditions of accidental radiation exposure. The exposure environment is ill defined and uncontrolled.3 The radiation delivery is heterogeneous and nonuniform, and may vary in rate, quality, and energy. It is the uncontrolled nature of the radiation exposure, in addition to the potential for shielding, that forecasts the possible sparing of cells essential for survival, i.e., the stem cells of the hematopoietic system and the gastrointestinal system. Radiation experiments in which areas of the bone marrow were shielded have demonstrated the potential of spared bone marrow cells to repopulate the hematopoietic tissue and to increase not only the production of granulocytes and platelets but also the chances of surviving an otherwise lethal dose of radiation.4–11

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Guskova, A. Biomedical Section of the Soviet Report on Chernobyl, Appendix 7, Medical Biological Problems, International Atomic Energy Agency (IAEA ), Vienna, 1986.

    Google Scholar 

  2. Roberts, L. Radiation accident grips Goiânia. Science 238: 1028–1031, 1989.

    Article  Google Scholar 

  3. Baverstock, K. F., and Ash, P. J. N. O. A review of radiation accidents involving whole body exposure and the relevance to the LD50160 for man. Br J Radio! 56: 837, 1983.

    Article  CAS  Google Scholar 

  4. Cole, L. J., Haire, H. M., and Alpen, E. L. Partial shielding of dogs: Effectiveness of small external epicondylar lead cuffs against lethal x-radiation. Radiat Res 32: 54–63, 1967.

    Google Scholar 

  5. Croizat, H., Frindel, E., and Tubiana, M. Abscopal effect of irradiation on haemopoietic stem cells of shielded bone marrow-role of migration. Int J Radiat Biol 30: 347–358, 1976.

    Article  CAS  Google Scholar 

  6. Gidali, J., and Lajtha, L. G. Regulation of hemopoietic stem cell turnover in partially irradiated mice. Cell Tissue Kinet 5: 147–157, 1972.

    CAS  Google Scholar 

  7. Hansen, C. L., Michaelson, S. M., and Howland, J. W. Lethality of upper body exposure to x-radiation in beagles. Public Health Rep 76: 242, 1961.

    Article  PubMed  Google Scholar 

  8. Knospe, W. H., Blom, J., and Crosby, W. H. Regeneration of locally irradiated bone marrow. I. Dose dependent, long-term changes in the rat, with particular emphasis upon vascular and stromal reaction. Blood 28: 398–415, 1966.

    PubMed  CAS  Google Scholar 

  9. Maillie, H. D., Krasavage, W., and Mermagen, H. On the partial body irradiation of the dog. Health Phys 12: 833–837, 1966.

    Article  Google Scholar 

  10. Maloney, M. A., and Patt, H. M. Migration of cells from shielded to irradiated marrow. Blood 39: 804–808, 1972.

    PubMed  CAS  Google Scholar 

  11. Nothdurft, W., Calvo, W., Klinnert, V., et al. Acute and long term alterations in the granulocyte/ macrophage progenitor cell (GM-CFC) compartment of dogs after partial-body irradiation. Int J Radiat Oncol Biol Phys 12: 949–957, 1986.

    CAS  Google Scholar 

  12. Broxmeyer, H. E., Williams, D. E., and Cooper, S. The influence in vivo of natural murine interleukin-3 on the proliferation of myeloid progenitor cells in mice recovering from sublethal dosages of cyclophosphamide. Leuk Res 11 (2): 201–205, 1987.

    Article  PubMed  CAS  Google Scholar 

  13. Cohen, A. M., Zsebo, K. M., Inoue, H., et al. In vivo stimulation of granulopoiesis by recombinant human granulocyte colony-stimulating factor. Proc Nat/ Acad Sci USA 84:2484–2488, 1987.

    Google Scholar 

  14. Fujisawa, M., Kobayashi, Y., Okabe, T., et al. Recombinant human granulocyte colony-stimulating factor induces granulocytosis in vivo. Jpn J Cancer Res 77: 866–869, 1986.

    PubMed  CAS  Google Scholar 

  15. Kindler, V., Thorens, B., deKossodo, S., et al. Stimulation of hematopoiesis in vivo by recombinant bacterial murine interleukin 3. Proc Natl Acad Sci USA 83: 1001–1005, 1986.

    Article  PubMed  CAS  Google Scholar 

  16. Kobayashi, Y., Okabe, T., Urabe, A., et al. Human granulocyte colony stimulating factor produced by Escherichia col/ shortens the period of granulocytopenia induced by irradiation in mice. Jpn J Cancer Res 78: 763–770, 1987.

    CAS  Google Scholar 

  17. Lord, B. I., Molineux, G., Testa, N. G., et al. The kinetic response of haemopoietic precursors cells, in vivo, to highly purified, recombinant interleukin 3. Lymphokine Res 5: 97–104, 1986.

    PubMed  CAS  Google Scholar 

  18. Metcalf, D., Begley, C. G., Johnson, G. R., et al. Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice. Blood 68: 46–57, 1986.

    PubMed  CAS  Google Scholar 

  19. Moore, M. A. S., and Warren, D. J. Synergy of interleukin-1 and granulocyte colony stimulating factor: In vivo stimulation of stem cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice. Proc Nat! Acad Sci USA 84: 7134–7138, 1987.

    Article  CAS  Google Scholar 

  20. Morrissey, P., Charrier, K., Bressler, L., et al. The influence of I L-1 treatment on the reconstitution of the hematopoietic and immune systems after sublethal radiation. J Immunol 140: 4204–4210, 1988.

    PubMed  CAS  Google Scholar 

  21. Shimamura, M., Kobayashi, Y., Yuo, A., et al. Effect of human recombinant granulocyte colony-stimulating factor on hemopoietic injury in mice induced by 5-fluorouracil. Blood 69: 353–355, 1987.

    PubMed  CAS  Google Scholar 

  22. Stork, L., Barczuk, L., Kissinger, M., et al. Interleukin-1 accelerates murine granulocyte recovery following treatment with cyclophosphamide. Blood 73: 938–944, 1989.

    PubMed  CAS  Google Scholar 

  23. Tamura, M., Hattori, K., Nomura, H., et al. Induction of neutrophilic granulocytosis in mice by administration of purified human native granulocyte colony-stimulating factor (G-CSF). Biochem Biophys Res Commun 142: 454–460, 1987.

    Article  PubMed  CAS  Google Scholar 

  24. Tanikawa, S., Nakao, I., Tsuneoka, K., et al. Effects of recombinant granulocyte colony stimulating factor (rG-CSF) and recombinant granulocyte-macrophage colony stimulating factor (rGMCSF) on acute radiation hematopoietic injury in mice. Exp Hematol 17: 883–888, 1989.

    PubMed  CAS  Google Scholar 

  25. Lam, C., Mayer, P., Besemer, J., et al. Differential activation of dog, human, and monkey peripheral blood granulocytes by recombinant human granulocyte-macrophage colony-stimulating factor, in vivo hematopoietic activity in dogs. J Cell Biochem [Suppl] 13c: H401 (Abstract), 1989.

    Google Scholar 

  26. Lothrup, C. D., Jr., Warren, D. J., Souza, L. M., et al. Connection of canine cyclic hematopoiesis with recombinant human granulocyte colony stimulating factor. Blood 72: 1324–1328, 1988.

    Google Scholar 

  27. MacVittie, T. J., D’Alesandro, M. M., Monroy, R. L., et al. Stimulation of hemopoiesis in the canine by in vivo administration of recombinant human GM-CSF (rhGM-CSF). J Cell Biochem [Suppl] 12A: 152 (Abstract), 1988.

    Google Scholar 

  28. MacVittie, T. J., Schwartz, G. N., Monroy, R. L., et al. Stimulation of hemopoiesis in the canine by administration of recombinant human interleukin-1. Exp Hematol 16: 537 (Abstract), 1988.

    Google Scholar 

  29. Schuening, F. G., Storb, R., Goehle, S., et al. Stimulation of canine hematopoiesis by recombinant human granulocyte-macrophage colony-stimulating factor. Exp Hematol 17: 889–894, 1989.

    CAS  Google Scholar 

  30. Schuening, F. G., Storb, R., Goehle, S., et al. Effect of recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoietic recovery after otherwise lethal total-body irradiation. Blood 74: 1308–1313, 1989.

    PubMed  CAS  Google Scholar 

  31. MacVittie, T. J., Monroy, R. L., Patchen, M. L., et al. Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation. Int J Radiat Bio157: 723–736, 1990.

    Google Scholar 

  32. Donahue, R. E., Wang, E. A., Stone, D. K., et al. Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF. Nature 321: 872–875, 1986.

    Article  PubMed  CAS  Google Scholar 

  33. Donahue, R. E., Seehra, J., Metzger, M., et al. Human IL-3 and GM-CSF act synergistically in stimulating hematopoiesis in primates. Science 241: 1820–1823, 1988.

    Article  PubMed  CAS  Google Scholar 

  34. Gasparetto, C., Laver, J., Abboud, M., et al. Effects of interleukin-1 on hemopoietic progenitors: Evidence of stimulatory and inhibitory activities in a primate model. Blood 74: 547–550, 1989.

    PubMed  CAS  Google Scholar 

  35. Krumwieh, D., and Seiler, F. R. In vivo effects of recombinant colony stimulating factors on hematopoiesis in cynomolgus monkeys. Transplant Proc 21:2964–2967, 1989.

    Google Scholar 

  36. Mayer, P., Lam, C., Obenaus, H., et al. Recombinant human GM-CSF induces leukocytosis and activates peripheral blood polymorphonuclear neutrophile in non-human primates. Blood 70: 206–213, 1987.

    PubMed  CAS  Google Scholar 

  37. Monroy, R. L., Skelly, R. R., Taylor, P., et al. Recovery from severe hemopoietic suppression using recombinant human granulocyte-macrophage colony-stimulating factor. Exp Hematol 16: 344–348, 1988.

    PubMed  CAS  Google Scholar 

  38. Welte, K., Bonilla, M. A., Gillio, A. P., et al. Recombinant human granulocyte colony-stimulating factor: Effects on hematopoiesis in normal and cyclophosphamide-treated primates. J Exp Med 165: 941–948, 1987.

    Article  CAS  Google Scholar 

  39. Souza, L. M., Boone, T. C., Gabrilove, J., et al. Recombinant human granulocyte colony-stimulating factor: Effects on normal and leukemic myeloid cells. Science 232: 61–65, 1986.

    Article  PubMed  CAS  Google Scholar 

  40. Monroy, R. L., MacVittie, T. J., Darden, J. H., et al. The rhesus monkey: A primate model for hemopoietic stem cell studies. Exp Hematol 14: 904–911, 1986.

    CAS  Google Scholar 

  41. MacVittie, T. J., Monroy, R. L., Patchen, M. L., et al. Acute lethality and radiosensitivity of the canine hemopoietic system to cobalt-60 gamma and mixed neutron-gamma irradiation. In: Response of Different Species to Total Body Irradiation. J. J. Broerse and T. J. MacVittie, Eds. Martinus Nijhoff Publishers, Dordrecht, Netherlands, 1984, pp. 113–129.

    Chapter  Google Scholar 

  42. Broerse, J. J., van Bekkum, D. W., Hollander, C. F., et al. Mortality of monkeys after exposure to fission neutrons and the effect of autologous bone marrow transplantation. Int J Radiat Biol 34: 253–264, 1978.

    Article  CAS  Google Scholar 

  43. Jackson, D. P., Sorenson, D. K., Cronkite, E. P., et al. Effectiveness of transfusion of fresh and lyophilized platelets in controlling bleeding due to thrombocytopenia. J Clin Invest 38: 1689 1697, 1959.

    Google Scholar 

  44. Perman, V., Cronkite, E. P., Bond, V. P., et al. The regenerative ability of hemopoietic tissue following lethal x-irradiation in dogs. Blood 19: 724–737, 1962.

    PubMed  CAS  Google Scholar 

  45. Sorenson, D. K., Bond, V. P., Cronkite, E. P., et al. An effective therapeutic regimen for the hemopoietic phase of the acute radiation syndrome in dogs. Radiat Res 13: 669–676, 1960.

    Article  Google Scholar 

  46. Ferrero, D., Tarella, C., Badoni, R., et al. Granulocyte-macrophage colony-stimulating factor requires interaction with accessory cells or granulocyte colony-stimulating factor for full stimulation of human myeloid progenitors. Blood 73: 402–405, 1989.

    PubMed  CAS  Google Scholar 

  47. McNiece, I. K., Andrews, R., Stewart, M., et al. Action of interleukin-3, G-CSF, and GMCSF on highly enriched human hematopoietic progenitor cells: Synergistic interaction of GMCSF plus G-CSF. Blood 74: 110–114, 1989.

    PubMed  CAS  Google Scholar 

  48. Ikebuchi, K., Clark, S. C., Ihle, J. N., et al. Granulocyte colony-stimulating factor enhances interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA 85: 3445–3450, 1988.

    Article  PubMed  CAS  Google Scholar 

  49. Broxmeyer, H. E., Williams, D. E., Hangoc, G., et al. Synergistic myelopoietic actions in vivo after administration to mice of combinations of purified natural murine colony-stimulating factor 1, recombinant murine interleukin 3, and recombinant murine granulocyte/macrophage colony-stimulating factor. Proc Natl Acad Sci USA 84: 3871–3875, 1987.

    Article  PubMed  CAS  Google Scholar 

  50. Williams, D. E., Hangoc, G., Cooper, S., et al. The effects of purified recombinant murine interleukin-3 and/or purified natural murine CSF-1 in vivo on the proliferation of murine high-and low-proliferative potential colony-forming cells: Demonstration of in vivo synergism. Blood 70 (2): 401–403, 1987.

    PubMed  CAS  Google Scholar 

  51. Vriesendorp, H. M., and van Bekkum, D. W. Susceptibility to total body irradiation. In: Response of Different Species to Total Body Irradiation. J. J. Broerse and T. J. MacVittie, Eds. Martinus Nijhoff Publishers, Dordrecht, Netherlands, 1984, pp. 43–57.

    Google Scholar 

  52. Butturini, A., DeSouza, P. C., Gale, R. P., et al. Use of recombinant granulocyte-macrophage colony stimulating factor in the Brazil radiation accident. Lancet 11: 471–475, 1988.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland, 20814-5145, USA

    Thomas J. MacVittie

  2. Immunobiology and Transplantation Branch, Naval Medical Research Institute, Bethesda, Maryland, 20814-5055, USA

    Rodney L. Monroy

Authors
  1. Thomas J. MacVittie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rodney L. Monroy
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, Bethesda, Maryland, USA

    Doris Browne , Joseph F. Weiss , Thomas J. MacVittie  & Madhavan V. Pillai , ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Springer Science+Business Media New York

About this chapter

Cite this chapter

MacVittie, T.J., Monroy, R.L. (1990). Rescue of Lethally Irradiated Animals. In: Browne, D., Weiss, J.F., MacVittie, T.J., Pillai, M.V. (eds) Treatment of Radiation Injuries. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0864-3_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-0864-3_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-0866-7

  • Online ISBN: 978-1-4899-0864-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation