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Effects of low level radiation upon the hematopoietic stem cell: Implications for leukemogenesis

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Summary

These studies have addressed firstly the effect of single small doses of x-rays upon murine hematopoietic stem cells to obtain a better estimate of theD q . It is small, of the order of 20 rad.

Secondly, a dose fractionation schedule that does not kill or perturb the kinetics of hemopoietic cell proliferation was sought in order to investigate the leukemogenic potential of low level radiation upon an unperturbed hemopoietic system. Doses used by others in past radiation leukemogenesis studies clearly perturb hemopoiesis and kill a detectable fraction of stem cells. The studies reported herein show that 1.25 rad every day decrease the CFU-S content of bone marrow by the time 80 rads are accumulated. Higher daily doses as used in published studies on radiation leukemogenesis produce greater effects.

Studies on the effect of 0.5, 1.0, 2.0, and 3.0 rad 3 times per week are under way. Two rad 3 times per week produced a modest decrease in CFU-S content of bone marrow after an accumulation of 68 rad. With 3.0 rad 3 times per week an accumulation of 102 rad produced a significant decrease in CFU-S content of bone marrow. Dose fractionation at 0.5 and 1.0 rad 3 times per week has not produced a CFU-S depression after accumulation of 17 and 34 rad.

Radiation leukemogenesis studies published to date have utilized single doses and chronic exposure schedules that probably have significantly perturbed the kinetics of hematopoietic stem cells. Whether radiation will produce leukemia in animal models with dose schedules that do not perturb kinetics of hematopoietic stem cells remains to be seen.

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References

  1. Ishimaru T, Hoshino T, Ichimaru M, et al. (1971) Leukemia in atomic bomb survivors. Radia Res 45:216–233

    Google Scholar 

  2. Court-Brown WM, Doll R Leukemia and aplastic anemia in patients irradiated for ankylosing spondylitis. Medical Research Council Special report No. 295 HMSO London, England

  3. Gray EH (1965) In: Cellular radiation biology 18th Annual Symposium on Fundamental Cancer Research, Williams and Wilkins, Baltimore, pp 7–25

    Google Scholar 

  4. Till JE, McCulloch EA (1961) A direct measurement of the radiation sensitivity of normal bone marrow cells. Radiat Res 14:213

    PubMed  Google Scholar 

  5. Becker AJ, McCulloch EA, Till JE (1936) Cytological demonstration of the clonal nature of spleen colonies derived from transplated mouse marrow cells. Nature 197:452–454

    Google Scholar 

  6. Till JE, McCulloch EA (1972) The (f) factor of the spleen colony assay for hemopoietic stem cells. Series Hematologica 14:213

    Google Scholar 

  7. Monette FC, DeMello JB (1979) The relationship between stem cell seeding efficiency and position in cell cycle. Cell Tissue Kinetics 12:161–175

    Google Scholar 

  8. Becker JA, McCulloch EA, Siminovitch L, Till JE (1965) The effect of differing demands for blood cell production or DNA synthesis by hemopoietic colony-forming cells. Blood 26:296

    PubMed  Google Scholar 

  9. Schofield R (1978) The relationship between the spleen colony-forming cells and the hemopoietic stem cell: a hypothesis. Blood Cells 4:7–27

    PubMed  Google Scholar 

  10. Carsten AL, Commerford SL, Cronkite EP (1977) The genetic and late somatic effects of chronic tritium ingestion in ice. Curr Top Radiat Res Q 12:212–224

    Google Scholar 

  11. Carsten AL, Cronkite EP (1979) Comparison of late effects of single X-ray exposure, chronic tritiated water ingestion, and chronic137CS gamma exposure in mice. International Symposium of Biological Implications of Radionuclides from Nuclear Industries, International Atomic Energy Agency, IAEA-SM-237/45, pp 269–276, Vienna, Austria

    Google Scholar 

  12. Cronkite EP, Carsten AL, Brecher G (1979) Hemopoietic stem cell niches, recovery from radiation and bone marrow transfusions, pp 486–496, Radiation Research, Proceedings of the 6th Congress of International Radiation Research, Editor, Okada, Toppan Printing Company, Tokyo, Japan

    Google Scholar 

  13. Schofield R, Dexter TM (1982) CFU-S repopulation after low dose whole body radiation. Radiat Res 89:607–617

    PubMed  Google Scholar 

  14. Bond VP (1984) Stochastic basis for dose-response curves, RBE and temporal dependence. In: Boice JD, Fraumeni JF Jr (eds) Radiation carcinogenesis: epidemiology and biological significance. Raven Press, New York

    Google Scholar 

  15. Hendry JH, Lajtha LG (1972) The response of hemopoietic colony-forming units to be repeated doses of X-rays. Radiat Res 52:300–315

    Google Scholar 

  16. Silini R, Elli R, Siracusa G, Pozzi LV (1968) Repopulation of the bone marrow stem cell compartment after irradiation. Cell Tissue Kinet 1:111–122

    Google Scholar 

  17. Hendry JH (1979) The dose-dependence of the split-dose response of marrow colony-forming units (CFU-S): similarity to other tissues. Int J Radiat Biol 36 (No. 6):631–637

    Google Scholar 

  18. Upton AC, Randolph ML, Conklin JW (with the collaboration of Katenbaum MA, Slater M, Melveille Jr GS, Conte FP, Sproul Jr JA (1970) Late effects of fast neutrons and gamma-rays in mice as influenced by the dose rate of irradiation: Induction of neoplasia. Radiat Res 41 (No 3):467–491

    PubMed  Google Scholar 

  19. Mole RH (1975) Ionizing radiation as a carcinogen: practical questions and academic pursuits. Br J Radiol 48:157–169

    PubMed  Google Scholar 

  20. Major IR, Mole RH (1978) Myeloid leukaemia in X-ray irradiated CBA mice. Nature 272:455–456 (30 March, 1978)

    PubMed  Google Scholar 

  21. Schofield R, Lajtha LG (1976) Cellular kinetics of erythropoiesis. In: Congenital Disorders of Erythropoiesis, Ciba Foundation Symposium 37, 1976, Elsevier/Excerpta Medica/North Holland, pp 3–24

    Google Scholar 

  22. Fujiwara Y, Tasumi M, Sasaki MS (1977) Cross-link repair in human cells and its possible defect in Fanconi's anemia cells. J Mol Biol 113:635–649

    PubMed  Google Scholar 

  23. Paterson MC, Smith BP, Lohman PHM, Anderson AK, Fishman L (1976) Defective excision reaire of -ray-damaged DNA in human (ataxia telangiectasia) fibroblasts. Nature 260:444–446

    PubMed  Google Scholar 

  24. Sasaki MS, Tonomura A (1973) A high susceptibility of Fanconi's anemia to chromosome breakage by DNA crosslinking agents. Cancer Res 33:1829–1936

    PubMed  Google Scholar 

  25. Murnane JP, Painter RB (1982) Complementation of the defects in DNA synthesis in irradiated and unirradiated ataxia-telangiectasia cells. Proc Natl Acad Sci (US) 79:1960–1963

    Google Scholar 

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Author notes

  1. M. E. Miller

    Present address: Division of Hematologic Research, The Memorial Hospital, 02860, Pawtucket, RI, USA

Authors and Affiliations

  1. Medical Department, Brookhaven National Laboratory, 11973, Upton, NY, USA

    E. P. Cronkite, V. P. Bond, A. L. Carsten, T. Inoue, M. E. Miller & J. E. Bullis

  2. Department of Pathology, Yokohama City University Medical School, Yokohama

    T. Inoue

Authors
  1. E. P. Cronkite
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  2. V. P. Bond
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  3. A. L. Carsten
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  4. T. Inoue
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  5. M. E. Miller
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  6. J. E. Bullis
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Additional information

Dedicated to Prof. L.E. Feinendegen on the occasion of his 60th birthday

Research supported by the U.S. Department of Energy under contract DE-ACO2-7 6CH00016. Accordingly, the U.S. government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. government purpose

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Cronkite, E.P., Bond, V.P., Carsten, A.L. et al. Effects of low level radiation upon the hematopoietic stem cell: Implications for leukemogenesis. Radiat Environ Biophys 26, 103–114 (1987). https://doi.org/10.1007/BF01211405

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  • DOI: https://doi.org/10.1007/BF01211405

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