The Radiobiology of In Vitro Neoplastic Transformation

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


The carcinogenic properties of ionizing radiation became evident within a few years of the discovery of X-rays by Roentgen, when the development of cancer in radiation ulcerations of the skin was observed in a number of early radiation workers. This phenomenon has since been confirmed in many cellular and animal models, in which it has been shown that radiation will induce cancer in most tissues of most mammalian species. Despite these observations, however, the molecular mechanisms for this effect remain obscure.


Chromosomal Rearrangement Neoplastic Transformation Linear Energy Transfer Relative Biological Effectiveness Irradiate Cell 
These keywords were added by machine and not by the authors.


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  1. 1.
    J. B. Little, Radiation transformation in vitro: implications for mechanisms of carcinogenesis, in: “Advances in Modern Environmental Toxicology, Vol. 1,” N. Mishra, V. Dnukel, and M. Mehlman, eds., Senate Press, Inc., New Jersey (1981), pp. 383–426.Google Scholar
  2. 2.
    J. C. Barrett and P. O. P. Ts’o, Evidence for the progressive nature of neoplastic transformation in vitro, Proc. Natl. Acad. Sci. USA, 75:3761–3765 (1978).PubMedCrossRefGoogle Scholar
  3. 3.
    Y. Berwold and L. Sachs, In vitro transformations of normal cells to tumor cells by carcinogenic hydrocarbons, J. Nat. Cancer Inst. 35:641–661 (1965).Google Scholar
  4. 4.
    C. A. Reznikoff, J. S. Bertram, D. W. Brankow, and C. Heidelberger, Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to post-confluence inhibition of cell division, Cancer Res. 33:3239–3249 (1973).PubMedGoogle Scholar
  5. 5.
    T. Kakunaga, A quantitative system for assay of malignant transformation by chemical carcinogens using a clone derived from BALB/3T3, Int. J. Cancer 12:463–473 (1973).PubMedCrossRefGoogle Scholar
  6. 6.
    T. C. H. Yang and C. A. Tobias, Radiation and cell transformation in vitro, Adv. Biol. Med. Phys. 17:417–461 (1980).PubMedGoogle Scholar
  7. 7.
    C. Borek, in: “Particle Radiation Therapy,” V. P. Smith, ed., Am. Coll. Radiology, Philadelphia, PA (1975), pp. 284–301.Google Scholar
  8. 8.
    A. Han and M. M. Elkind, Transformation of mouse C3H 10T1/2 cells by single and fractionated doses of X-rays and fission-spectrum neutrons, Cancer Res. 39:123–130 (1979).PubMedGoogle Scholar
  9. 9.
    J. B. Robertson, A. Koehler, J. George, and J. B. Little, Oncogenic transformation of mouse BALB/3T3 cells by plutonium-238 alpha particles, Radiat. Res. 96:261–274 (1983).PubMedCrossRefGoogle Scholar
  10. 10.
    C. K. Hill, F. M. Buonaguro, C. P. Myers, A. Han, and M. M. Elkind, Fission-spectrum neutrons at reduced dose rates enhance neoplastic transformation, Nature 298:67–69 (1982).PubMedCrossRefGoogle Scholar
  11. 11.
    C. Borek and E. J. Hall, Effect of split doses of X-rays on neoplastic transformation of single cells, Nature 252:499–501 (1976).CrossRefGoogle Scholar
  12. 12.
    M. Terzaghi, and J. B. Little, Oncogenic transformation in vitro after split dose X-irradiation, Int. J. Radiat. Biol. 29:583–587 (1976).CrossRefGoogle Scholar
  13. 13.
    R. Miller and E. J. Hall, X-ray dose fractionation and oncogenic transformation in cultured mouse embryo cells, Nature, 272:58–60 (1978).PubMedCrossRefGoogle Scholar
  14. 14.
    J. B. Little, Quantitative studies of radiation transformation with the A31-11 mouse BALB/3T3 cell line, Cancer Res. 39:1478–1484 (1979).Google Scholar
  15. 15.
    E. J. Hall and R. C. Miller, The how and the why of in vitro oncogenic transformation, Radiat. Res. 87:208–223 (1981).PubMedCrossRefGoogle Scholar
  16. 16.
    A. Han, C. K. Hill, and M. M. Elkind, Repair of cell killing and neoplastic transformation at reduced dose rates of 60Co gamma-rays, Cancer Res. 40:3328–3332 (1980).PubMedGoogle Scholar
  17. 17.
    J. B. Little, Influence of noncarcinogenic secondary factors on radiation carcinogenesis, Radiat. Res. 87:240–250 (1981).PubMedCrossRefGoogle Scholar
  18. 18.
    A. R. Kennedy, G. Murphy, and J. B. Little, The effect of time and duration of exposure to 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on X-ray transformation of C3H 10T1/2 cells, Cancer Res. 40:1915–1920 (1980).PubMedGoogle Scholar
  19. 19.
    A. R. Kennedy and J. B. Little, Protease inhibitors suppress radiation induced malignant transformation in vitro, Nature 276:825–826 (1978).PubMedCrossRefGoogle Scholar
  20. 20.
    L. Harisiadis, R. C. Miller, E. J. Hall, and C. A. Borek. A vitamin A analogue inhibits radiation-induced oncogenic transformation, Nature 274:486–487 (1978).PubMedCrossRefGoogle Scholar
  21. 21.
    H. Nagasawa and J. B. Little, Factors influencing the induction of sister chromatid exchanges in mammalian cells by 12-0-tetradecanoyl-phorbol-13-acetate, Carcinogenesis 2:601–607 (1981).PubMedCrossRefGoogle Scholar
  22. 22.
    I. Emerit and P. A. Cerutti, Tumor promoter phorbol 12-myristate-13-acetate induces a clastogenic factor in human lymphocytes, Proc. Natl. Acad. Sci. USA 79:7509–7513 (1982).PubMedCrossRefGoogle Scholar
  23. 23.
    A. R. Kennedy, M. Fox, G. Murphy, and J. B. Little, Relationship between X-ray exposure and malignant transformation in C3H 10T1/2 cells, Proc. Natl. Acad. Sci. USA 77:7262–7266 (1980).PubMedCrossRefGoogle Scholar
  24. 24.
    A. R. Kennedy and J. B. Little, Investigation of the mechanisms for enhancement of radiation transformation in vitro by 12-0-tetradecanoyl-phorbol-13-acetate, Carcinogenesis 1:1039–1047 (1980).PubMedCrossRefGoogle Scholar
  25. 25.
    J. M. Backer, M. Boerzig, and I. B. Weinstein, When do carcinogentreated 10T1/2 cells acquire the commitment to form transformed foci?, Nature 299:458–460 (1982).PubMedCrossRefGoogle Scholar
  26. 26.
    E. J. Hall, H. H. Rossi, M. Zaider, R. C. Miller, and C. Borek, The role of neutrons in cell transformation research: II, experimental, in: “Neutron Carcinogenesis,” J. J. Broerse and G. B. Gerber, eds., Commission of the European Communities, Luxembourg (1982), pp. 371–395.Google Scholar
  27. 27.
    A. R. Kennedy, J. Cairns, and J. B. Little, Timing of the steps in transformation of C3H 10T1/2 cells by X-irradiation, Nature 307:85–86 (1984).PubMedCrossRefGoogle Scholar
  28. 28.
    A. R. Kennedy and J. B. Little, Evidence that a second event in X-ray induced oncogenic transformation in vitro occurs during cellular proliferation, Radiat. Res. 99:228–248 (1984).PubMedCrossRefGoogle Scholar
  29. 29.
    D. E. Lea and C. A. Coulson, The distribution of the numbers of mutants in bacterial populations, J. Genet. 49:264–285 (1949).CrossRefGoogle Scholar
  30. 30.
    P. K. LeMotte, S. J. Adelstein, and J. B. Little, Malignant transformation induced by incorporated radionuclides in BALB/3T3 mouse embryo fibroblasts, Proc. Natl. Acad. Sci. USA 79:7763–7767 (1982).PubMedCrossRefGoogle Scholar
  31. 31.
    P. K. LeMotte and J. B. Little, DNA damage induced in human diploid cells by decay of incorporated radionuclides, Cancer Res. 44:1337–1342 (1984).PubMedGoogle Scholar
  32. 32.
    H. L. Liber, P. K. LeMotte, and J. B. Little, Toxicity and mutagenicity of X-rays, (125)dUrd or (3H)TdR incorporated in the DNA of human lymphoblast cells, Mutation Res. 111:387–404 (1983).PubMedCrossRefGoogle Scholar
  33. 33.
    A. R. Kennedy, Evidence that the first step leading to carcinogeninduced malignant transformation is a high frequency common event, in: “Cell Transformation Assays: Application to Studies of Mechanisms of Carcinogenesis and to Carcinogen Testing,” J. C. Barrett, ed., Raven Press, New York, in press.Google Scholar
  34. 34.
    M. Terzaghi and P. Nettesheim, Dynamics of neoplastic development in carcinogen-exposed tracheal mucosa, Cancer Res. 39:4003–4010 (1979).PubMedGoogle Scholar
  35. 35.
    S. P. Ethier and R. L. Ullrich, Detection of ductal dysplasia in mammary outgrowths derived from carcinogen-treated virgin female BALB/c mice, Cancer Res. 42:1753-1760.Google Scholar
  36. 36.
    K. H. Clifton, K. Kamiya, R. T. Mulcahy, and M. N. Gould, Radiogenic neoplasia in the thyroid and mammary clonogens: progress, problems and possibilities, in: “Symposium Proceedings, Estimation of Risk from Low Doses of Radiation and Chemicals: A Critical Overview,” Brookhaven National Laboratory (May 20–23, 1984).Google Scholar
  37. 37.
    R. T. Mulcahy, M. N. Gould, and K. H. Clifton. Radiogenic initiation of thyroid cancer: a common cellular event, Int. J. Radiat. Biol. 45:419–426 (1984).CrossRefGoogle Scholar
  38. 38.
    J. B. Little, Mechanisms of malignant transformation of human diploid cells, in: “Carcinogenesis: A Comprehensive Survey, Vol 10; The Role of Chemicals and Radiation in the Etiology of Cancer,” E. Huberman, ed., Raven Press, New York (1985), pp. 337–353.Google Scholar
  39. 39.
    T. Kakunaga, Neoplastic transformation of human diploid fibroblast cells by chemical carcinogens, Proc. National Acad. Sci. USA 75:1334–1338 (1978).CrossRefGoogle Scholar
  40. 40.
    G. Milo and J. A. DiPaolo, Neoplastic transformation of human diploid cells in vitro after chemical carcinogen treatment, Nature (Lond.) 275:130–132 (1978).CrossRefGoogle Scholar
  41. 41.
    K. C. Silinskas, S. A. Kateley, J. E. Tower, V. M. Maher, and J. J. McCormick, Induction of anchorage-independent growth in human fibroblasts by propane sultone Cancer Res. 41:1620–1627 (1981).PubMedGoogle Scholar
  42. 42.
    C. Borek, X-ray-induced in vitro neoplastic transformation of human diploid cells, Nature(Lond.) 283:776–778 (1980).CrossRefGoogle Scholar
  43. 43.
    R. J. Zimmerman and J. B. Little, Characterization of a quantitative assay for the in vitro transformation of normal human diploid fibroblasts to anchorage independence by chemical carcinogens, Cancer Res. 43:2176–2182 (1983).PubMedGoogle Scholar
  44. 44.
    R. J. Zimmerman and J. B. Little, Characteristics of human diploid fibroblasts transformed in vitro by chemical carcinogens, Cancer Res. 43:2183–2189 (1983).PubMedGoogle Scholar
  45. 45.
    Y. Kano and J. B. Little, Persistence of X-ray-induced chromosomal rearrangements in long-term cultures of human diploid fibroblasts, Cancer Res. 44:3706–3711 (1984).PubMedGoogle Scholar
  46. 46.
    A. J. Fornace, Jr., H. Nagasawa, and J. B. Little, Relationship of DNA repair to chromosome aberrations, sister chromatid exchanges and survival during liquid holding recovery in X-irradiated mammalian cells, Mutation Res. 70:323–336 (1980).PubMedCrossRefGoogle Scholar
  47. 47.
    Y. Kano and J. B. Little. Mechanisms of human cell neoplastic transformation: X-ray-induced abnormal clone formation in long-term cultures of human diploid fibroblasts. Cancer Res. 45:2550–2555 (1985).PubMedGoogle Scholar
  48. 48.
    Y. Kano and J. B. Little. Mechanisms of human cell neoplastic transformations: relationship of specific abnormal clone formation to prolonged lifespan in X-irradiated human diploid fibroblasts. Int. J. Cancer. 36:407–413 (1985).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • J. B. Little
    • 1
  1. 1.Laboratory of Radiobiology, Department of Cancer BiologyHarvard School, Public HealthBostonUSA

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