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Tumour Induction in Experimental Animals after Neutron and X-Irradiation

  • J. J. Broerse
Part of the NATO ASI Series book series (NSSA, volume 124)

Abstract

Cancer induction is generally considered to be the most important somatic effect of low dose ionizing radiation. It is therefore of great concern to obtain information on the dose-response relationships for carcinogenesis and to assess the quantitative cancer risk of exposure to radiations of different quality.

Tissues in the human with a high sensitivity for cancer induction include the bone marrow, the lung, the thyroid and the breast in women. If the revised dosimetry estimates for the Japanese survivors of the atomic bomb explosions are correct, there is no useful data base left to derive RBE values for human carcinogenesis. As a consequence, it will be necessary to rely on results obtained in biological systems, including experimental animals, for these estimates.

The following aspects of experimental studies on radiation carcinogenesis are of relevance:
  1. 1.

    Assessment of the nature of dose-response relationships.

     
  2. 2.

    Determination of the relative biological effectiveness of radiations of different quality.

     
  3. 3.

    Effects of fractionation or protraction of the dose on tumour development.

     

For the analysis of tumour data in animals, specific approaches, such as nonparametric actuarial methods and proportional hazard functions, have to be applied. The dose response curves for radiation induced cancer in different tissues vary in shape. This is exemplified by studies on myeloid leukemia in mice and mammary neoplasms in different rat strains. The results on radiation carcinogenesis in animal models clearly indicate that the highest RBE values are observed for neutrons with energies between 0.5 and 1 MeV.

The diversity of dose-response relationships point to different mechanisms involved in the induction of different tumours in various species and even in different strains of the same species.

Keywords

Linear Energy Transfer Relative Biological Effectiveness Fission Neutron Neutron Dose Radiation Carcinogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    United Nations Scientific Committee on the Effects of Atomic Radiation, “Sources and Effects of Ionizing Radiation, ” United Nations, New York (1977).Google Scholar
  2. 2.
    J. J. Broerse, C. F. Hollander, and M. J. van Zwieten, Tumour induction in Rhesus monkeys after total body irradiation with X-rays and fission neutrons, Int. J. Radiat. Biol. 40:671–676 (1981).CrossRefGoogle Scholar
  3. 3.
    H. J. Deeg, R. Prentice, T. E. Fritz, G. E. Sale, L. S. Lombard, E. D. Thomas, and R. Storb, Increased incidence of malignant tumours in dogs after total body irradiation and marrow transplantation, Int. J. Radiat. Oncol. Biol. Phys. 9:1505–1511 (1983).PubMedCrossRefGoogle Scholar
  4. 4.
    ICRP Publication 26, “Recommendations of the International Commission on Radiological Protection, ” Pergamon Press (1977).Google Scholar
  5. 5.
    ICRP Publications 15 and 21, “Protection against Ionizing Radiation from External Sources and Data for Protection against Ionizing Radiation from External Sources. Recommendations of the International Commission on Radiological Protection, ” Pergamon Press (1976).Google Scholar
  6. 6.
    B. R. L. Siebert, R. S. Caswell, and J. J. Coyne, Calculations of quality factors for fast neutrons in materials composed of H, C, N and O, in: “Proc. Eighth Symposium on Microdosimetry, ” EUR 8395, J. Booz, and H. G. Ebert, eds., Commission of the European Communities, Luxemburg, (1983), pp. 1131–1140.Google Scholar
  7. 7.
    ICRU Report 26, “Neutron Dosimetry for Biology and Medicine, ” International Commission on Radiation Units and Measurements, ICRU, Washington (1977).Google Scholar
  8. 8.
    Committee on the Biological Effects of Ionizing Radiations, “The Effects on Populations of Exposure to Low Levels of Ionizing Radiation, ” National Academy Press, Washington (1980).Google Scholar
  9. 9.
    W. E. Loewe, and E. Mendelsohn, Revised dose estimates at Hiroshima and Nagasaki, Health Phys. 41:663–666 (1981).PubMedGoogle Scholar
  10. 10.
    G. D. Kerr, Review of dosimetry for the atomic bomb survivors, in: Proc. Fourth Symposium on Neutron Dosimetry, Vol. 1, “ EUR 7448, G. Burger, and H. G. Ebert, eds., Commission of the European Communities (1983), pp. 501-513.Google Scholar
  11. 11.
    “Reassessment of Atomic Bomb Radiation Dosimetry in Hiroshima and Nagasaki, ” Proc. Workshop held at Nagasaki, D. J. Thompson, ed., (1983).Google Scholar
  12. 12.
    “Reassessment of Atomic Bomb Radiation Dosimetry in Hiroshima and Nagasaki, with Special Reference to Shielding and Organ Doses, ” Proc. Workshop held at Hiroshima (1983).Google Scholar
  13. 13.
    W. K. Sinclair, Revisions in the dosimetry of atomic bomb survivors, in: “Proc. Seventh International Congress of Radiation Research, ” J. J. Broerse, G. W. Barendsen, H. B. Kal, and A. J. van der Kogel, eds., Martinus Nijhoff (1983), pp. 63-73.Google Scholar
  14. 14.
    R. Lowrey Dobson, and T. Straume, Cancer risks and neutron RBE’s from Hiroshima and Nagasaki, In: “Neutron Carcinogenesis, ” EUR 8084, J. J. Broerse, and G. B. Gerber, eds., Commission of the European Communities (1982), pp. 279-300.Google Scholar
  15. 15.
    H. H. Rossi, and C. W. Mays, Leukemia risk from neutrons, Health Phys. 34:353–360 (1978).PubMedCrossRefGoogle Scholar
  16. 16.
    G. W. Barendsen, Summary of round table discussion on neutron carcinogenesis and implication for radiation protection, in: “Neutron Carcinogenesis, ” EUR 8084, J. J. Broerse and G. B. Gerber, eds., Commission of the European Communities (1982), pp. 445-453.Google Scholar
  17. 17.
    R. Lawrey Dobson, and T. Straume, Hiroshima and Nagasaki: expanded radiobiological analysis and dose reconciliation, in: “Proc. Seventh International Congress of Radiation Research,” J. J. Broerse, G. W. Barendsen, H. B. Kal, and A. J. van der Kogel, eds., Martinus Nijhoff (1983), pp. C8-05.Google Scholar
  18. 18.
    J. I. Fabrikant, The BEIR III controversy, Radiat. Res. 84:361–368 (1980).PubMedCrossRefGoogle Scholar
  19. 19.
    E. P. Radford, Human health effects of low doses of ionizing radiation: the BEIR III controversy, Radiat. Res. 84:369–394 (1980).PubMedCrossRefGoogle Scholar
  20. 20.
    H. H. Rossi, Comments on the somatic effects section of the BEIR III report, Radiat. Res. 84:395–406 (1980).PubMedCrossRefGoogle Scholar
  21. 21.
    H. P. Leenhouts, and K. H. Chadwick, Association between stochastic and non-stochastic effects and cellular damage, in: “Biological Effects of Low-level Radiation, ” IAEA, Vienna (1983), pp. 129–138.Google Scholar
  22. 22.
    A. M. Kellerer, and H. H. Rossi, The theory of dual radiation action, Current Topics Radiat. Res. 8:85–158 (1972).Google Scholar
  23. 23.
    H. H. Rossi, E. J. Hall, and M. Zaider, The role of neutrons in cell transformation research, in: “Neutron Carcinogenesis, ” EUR 8084, J. J. Broerse, and G. B. Gerber, eds., Commission of the European Communities (1982), pp. 371-380.Google Scholar
  24. 24.
    H. H. Rossi, Microdosimetry and carcinogenesis, in: “Proc. Eighth Symposium on Microdosimetry, ” J. Booz, and H. G. Ebert, eds., Commission of the European Communities (1983), pp. 539-549.Google Scholar
  25. 25.
    G. W. Barendsen, Influence of radiation quality on the effectiveness of small doses for induction of reproductive death and chromosome aberrations in mammalian cells, Int. J. Radiat. Biol. 36:49–63 (1979).CrossRefGoogle Scholar
  26. 26.
    D. T. Goodhead, J. Thacker, and R. Cox, The conflict between the biological effects of ultrasoft X-rays and microdosimetric measurements and application, in: “Proc. Sixth Symposium on Microdosimetry, ” Vol. II, J. Booz and H. G. Ebert, eds., Commission of the European Communities (1978), pp. 829-843.Google Scholar
  27. 27.
    D. T. Goodhead, Deductions from cellular studies of inactivation, mutagenesis, and transformation, in: “Radiation Carcinogenesis: Epidemiology and Biological Significance,” J. D. Boice, Jr., and F. Fraumeni, Jr., eds., Raven Press, New York (1984), pp. 369–385.Google Scholar
  28. 28.
    G. W. Barendsen, Effects of radiation on the reproductive capacity and proliferation of cells in relation to carcinogenesis, in: “Radiation Carcinogenesis” A. C. Upton, R. E. Albert, F. J. Burns and R. E. Shore, eds., Elsevier, New York (1986) pp. 85–105.Google Scholar
  29. 29.
    D. W. van Bekkum, and P. Bentvelzen, The concept of gene transfermisrepair mechanism of radiation carcinogenesis may challenge the linear extrapolation model of risk estimation for low radiation doses, Health Phys. 43:231–237 (1982).PubMedCrossRefGoogle Scholar
  30. 30.
    J. W. Baum, Clonal theory of radiation carcinogenesis, in: “Proc. Eighth Symposium on Microdosimetry,” J. Booz, and H. G. Ebert, eds., Commission of the European Communities (1983), pp. 575-584.Google Scholar
  31. 31.
    C. J. Shellabarger, R. D. Brown, A. R. Rao, J. P. Shanley, V. P. Bond, A. M. Kellerer, H. H. Rossi, L. J. Goodman and R. E. Mills, Rat mammary carcinogenesis following neutron or X-radiation, in: “Proc. Symposium Biological Effects of Neutron Irradiation,” IAEA, Vienna (1974), pp. 391–401.Google Scholar
  32. 32.
    H. H. Vogel, Jr., High let irradiation of Sprague-Dawley female rats and mammary neoplasm induction, in: “Proc. Symposium Late Biological Effects of Ionizing Radiation,” Vol. II, IAEA, Vienna (1978), pp. 147–164.Google Scholar
  33. 33.
    H. H. Vogel, Jr., and H. W. Dickson, Mammary neoplasia in Sprague-Dawley rats following acute and protracted irradiation, in: “Neutron Carcinogenesis,” EUR 8084, J. J. Broerse and G. B. Gerber, eds., Commission of the European Communities (1982), pp. 135-154.Google Scholar
  34. 34.
    H. H. Rossi, and E. J. Hall, The multicellular nature of radiation carcinogenesis, in: Radiation Carcinogenesis: Epidemiology and Biological Significance, “ J. D. Boice, Jr., and J. F. Fraumeni, Jr., eds., Raven Press, New York (1984), pp. 359–367.Google Scholar
  35. 35.
    R. H. Mole, Dose-response relationships, in: “Radiation Carcinogenesis: Epidemiology and Biological Significance,” J. D. Boice, Jr., and J. F. Fraumeni, Jr., eds., Raven Press, New York (1984), pp. 403–420.Google Scholar
  36. 36.
    E. L. Kaplan and P. Meier, Nonparametric estimation from incomplete observations, J. Amer. Stat. Assoc. 53:457–481 (1958).CrossRefGoogle Scholar
  37. 37.
    C. J. Shellabarger, D. Chmelevsky, and A. M. Kellerer, Induction of mammary neoplasms in the Sprague-Dawley rat by 430-keV neutrons and X-rays, JNCI 64:821–833 (1980).PubMedGoogle Scholar
  38. 38.
    J. J. Broerse, S. Knaan, D. W. van Bekkum, C. F. Hollander, A. L. Nooteboom, and M. J. van Zwieten, Mammary carcinogenesis in rats after X-and neutron irradiation and hormone administration, in: “Proc. Symposium Late Biological Effects of Ionizing Radiation,” Vol. II, IAEA, Vienna (1978), pp. 13–27.Google Scholar
  39. 39.
    A. M. Kellerer, and D. Chmelevsky, Analysis of tumour rates and incidences—a survey of concepts and methods, in: “Neutron Carcinogenesis,” EUR 8084, J. J. Broerse, and G. B. Gerber, eds., Commission of the European Communities (1982), pp. 209-231.Google Scholar
  40. 40.
    J. D. Kalbfleisch and R. L. Prentice, “The Statistical Analysis of Failure Time Data,” John Wiley and Sons, New York (1980).Google Scholar
  41. 41.
    R. Peto, M. C. Pike, N. E. Day, R. G. Gray, P. N. Lee, S. Parish, J. Peto, S. Richards, and J. Wahrendorf, Guidelines for simple, sensitive significance tests for carcinogenic effects in long-term animal experiments, in: “IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Suppl. 2, Long-Term and Short-Term Screening Assays for Carcinogens: A Critical Appraisal,” IARC, Lyon (1980), pp. 311–423.Google Scholar
  42. 42.
    J. J. Broerse, L. A. Hennen, M. J. van Zwieten, and C. F. Hollander, Mammary carcinogenesis in different rat strains after single and fractionated irradiations, in: “Neutron Carcinogenesis,” EUR 8084, J. J. Broerse, and G. B. Gerber, eds., Commission of the European Communities (1982), pp. 155-168.Google Scholar
  43. 43.
    H. H. Rossi, The role of the theory of dual radiation action in radiation protection, in: “Advances in Radiation Protection and Dosimetry in Medicine,” R. H. Thomas, and V. Perez-Mendez, eds., Plenum Press, New York (1980), pp. 131–141.Google Scholar
  44. 44.
    M. J. van Zwieten, The rat as animal model in breast cancer research, Martinus Nijhoff (1984).Google Scholar
  45. 45.
    J. J. Broerse, L. A. Hennen, M. J. van Zwieten, and C. F. Hollander, Dose-effect relations for mammary carcinogenesis in different rat strains after irradiation with X-rays and monoenergetic neutrons, in: “Proc. Symposium Biological Effects of Low-Level Radiation,” IAEA, Vienna (1983), pp. 507–519.Google Scholar
  46. 46.
    M. J. van Zwieten, C. J. Shellabarger, C. F. Hollander, D. V. Cramer, J. P. Stone, S. R. Holtzman, and J. J. Broerse, Differences in DMBA-induced mammary neoplastic responses in two lines of Sprague-Dawley rats, Eur. J. Cancer Clin. Oncol. 20:1199–1204 (1984).PubMedCrossRefGoogle Scholar
  47. 47.
    H. H. Vogel, Jr., and J. E. Turner, Genetic component in rat mammary carcinogenesis, Radiat. Res. 89:264–273 (1982).PubMedCrossRefGoogle Scholar
  48. 48.
    A. C. Upton, F. F. Wolff, J. Furth, and A. W. Kimball, A comparison of the induction of myeloid and lymphoid leukemias in X-ratiated RF mice, Cancer Res. 18:842–848 (1958).PubMedGoogle Scholar
  49. 49.
    A. C. Upton, M. L. Randolph, and J. W. Conklin, Late effects of fast neutrons and gamma-rays in mice as influenced by the dose rate of irradiation: induction of neoplasia, Radiat. Res. 41:467–491 (1970).PubMedCrossRefGoogle Scholar
  50. 50.
    G. W. Barendsen, Fundamental aspects of cancer induction in relation to the effectiveness of small doses of radiation, in: “Proc. Symposium Late Biological Effects of Ionizing Radiation,” Vol. II, IAEA, Vienna (1978), pp. 263–275.Google Scholar
  51. 51.
    Mole, R. H., and J. A. G. Davids, Induction of myeloid leukaemia and other tumours in mice by irradiation with fission neutrons, in: “Neutron Carcinogenesis,” EUR 8084, J. J. Broerse, and G. B. Gerber, eds., Commission of the European Communities (1982), pp. 31-39.Google Scholar
  52. 52.
    R. L. Ullrich, M. C. Jernigan, and L. M. Adams, Induction of lung tumors in RFM mice after localized exposures to X-rays or neutrons, Radiat. Res. 80:464–473 (1979).PubMedCrossRefGoogle Scholar
  53. 53.
    R. L. Ullrich, Lung tumour induction in mice: neutron RBE at low closes, in: “Neutron Carcinogenesis,” EUR 8084, J. J, Broerse, and G. B. Gerber, eds., Commission of the European Communities (1982), pp. 43-55.Google Scholar
  54. 54.
    J. F. Thomson, L. S. Lombard, D. Grahn, F. S. Williamson, and T. E. Fritz, RBE of fission neutrons for life shortening and tumourigenesis, in: “Neutron Carcinogenesis,” EUR 8084, J. J. Broerse, and G. B. Gerber, eds., Commission of the European Communities (1982), pp. 75-93.Google Scholar
  55. 55.
    F. J. M. Fry, Experimental radiation carcinogenesis: what have we learned?, Radiat. Res. 87:224–239 (1981).PubMedCrossRefGoogle Scholar
  56. 56.
    C. Borek, and E. J. Hall, Induction and modulation of radiogenic transformation in mammalian cells, in: “Radiation carcinogenesis: Epidemiology and Biological Significance,” J. D. Boice, Jr., and J. F. Fraumeni, Jr., eds., Raven Press, New York (1984), pp. 291–302.Google Scholar
  57. 57.
    C. J. Shellabarger, D. Chmelevsky, A. M. Kellerer, and J. P. Stone, Induction of mammary neoplasms in the ACI rat by 430-keV neutrons, X-rays, and diethylstilbestrol, JNCI 69:1135–1146 (1982).PubMedGoogle Scholar
  58. 58.
    V. Covelli, V. diMajo, B. Bassani, S. Rebessi, M. Coppola, and G. Silini, Influence of age on life shortening and tumour induction after X-ray and neutron irradiation, Radiat. Res., 100, 348–364 (1984).PubMedCrossRefGoogle Scholar
  59. 59.
    M. M. Elkind, A. Han, and C. K. Hill, Error-free and error-prone repair in radiation-induced neoplastic cell transformation, in: “Radiation Carcinogenesis: Epidemiology and Biological Significance,” J. D. Boice Jr., and J. F. Fraumeni, Jr., eds., Raven Press, New York (1984), pp. 303–318.Google Scholar
  60. 60.
    J. B. Little, Radiation transformation in vitro/review, in: “Proc. Seventh International Congress of Radiation Research,” J. J. Broerse, G. W. Barendsen, H. B. Kal, and A. J. van der Kogel, eds., Martinus Nijhoff (1983), pp. 377-384.Google Scholar
  61. 61.
    R. L. Ullrich, Tumor induction in BALB/c mice after fractionated or protracted exposures to fission-spectrum neutrons, Radiat. Res. 97:587–597 (1984).PubMedCrossRefGoogle Scholar
  62. 62.
    NCRP Statement on Dose Limit for Neutrons (1980).Google Scholar
  63. 63.
    J. B. Storer, and T. J. Mitchell, Limiting values for the RBE of fission neutrons at low doses for life shortening in mice, Radiat. Res. 97:396–406 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • J. J. Broerse
    • 1
  1. 1.Radiobiological Institute TNORijswijkThe Netherlands

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