Radiation Research: Survival Kinetics

  • L. J. Tolmach
  • L. E. Hopwood
Part of the Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology book series (HEP, volume 38 / 1)


The lethal action of ionizing radiations on mammalian cells has been observed for almost as long as the existence of these radiations has been known, but even today, with a large body of experimental observations at our disposal, understanding of the mechanisms by which the initial deposition of energy and breakage of chemical bonds lead to cell death is far from complete. Nevertheless, significant progress has been made in recent years, largely through the application of kinetic analysis. This discussion will be restricted mainly to kinetic aspects of cell killing by x- and γ-rays; only cursory consideration will be given to the molecular bases of the phenomena and the cellular organelles involved. It will be apparent that many of the concepts and experimental approaches mentioned apply also to the lethal action of cytotoxic drugs.


Linear Energy Transfer Relative Biological Effectiveness Bone Marrow Stem Cell Irradiate Cell Chinese Hamster Cell 
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  1. Alpbe, T., Fowler, J.F., Morgan, R.L., Vonberg, D.D., Ellis, F., Oliver, R.: The characterization of the “type C” survival curve. Brit. J. Radiol. 35, 722–723 (1962).CrossRefGoogle Scholar
  2. Barendsen, G.W.: Dose survival curves of human cells in tissue culture irradiated with alpha-, beta-, 20kV x-, and 200 kV x-radiation. Nature (Lond.) 193, 1153–1155 (1962).CrossRefGoogle Scholar
  3. Barbndsen, G.W., Bbuskbr, L. J., Vergroesbn, A. J., Bxtdke, L.: Effects of different ionizing radiations on human cells in tissue culture. II. Biological experiments. Radiat. Res. 13, 841–849 (1960).CrossRefGoogle Scholar
  4. Barendsen, G.W., Walter, H.M.D., Fowler, J.F., Bewley, D.K.: Effects of different ionizing radiations on human cells in tissue culture. III. Experiments with cyclotron-accelerated alpha-particles and deuterons. Radiat. Res. 18, 106–119 (1963).PubMedCrossRefGoogle Scholar
  5. Bender, M.A., Gooch, P.G.: The kinetics of x-ray survival of mammalian cells in vitro. Int. J. Radiat. Biol. 5, 133–145 (1962).PubMedCrossRefGoogle Scholar
  6. Berry, R. J., Oliver, R.: Effect of post-irradiation incubation conditions on recovery between fractionated doses of x-rays. Nature (Lond.) 201, 94–96 (1964).CrossRefGoogle Scholar
  7. Bond, V.R., Fliedner, T.M., Archambeau, J.O.: Mammalian radiation lethality. New York and London: Academic 1965.Google Scholar
  8. Bond, V.P., Suit, H.D., Marcial, V. (Eds.): Time and dose relationships in radiation biology as applied to radiotherapy. Upton, N. Y.: Brookhaven National Laboratory 1970.Google Scholar
  9. Bruce, W.R., Van Der Gaag, H.: A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature (Lond.) 199, 79–80 (1963).CrossRefGoogle Scholar
  10. Chaffey, J.T., Hellman, S.: Differing responses to radiation of murine bone marrow stem cells in relation to the cell cycle. Cancer Res. 31, 1613–1615 (1971).PubMedGoogle Scholar
  11. Dewey, D.L.: The x-ray sensitivity of Serratia marcescens. Radiat. Res. 19, 64–87 (1963).PubMedCrossRefGoogle Scholar
  12. Dewey, W.C., Humphrey, R.M.: Restitution of radiation-induced chromosomal damage in Chinese hamster cells related to cell’s life cycle. Exp. Cell Res. 35, 262–276 (1964).PubMedCrossRefGoogle Scholar
  13. Djordjevic, B., Szybalsky, W.: Genetics of human cell lines. III. Incorporation of 5-bromo-and 5-iododeoxyuridine into the deoxyribonucleic acid of human cell lines and its effects on radiation sensitivity. J. exp. Med. 112, 509–531 (1960).PubMedCrossRefGoogle Scholar
  14. Elkind, M.M.: Sedimentation of DNA released from Chinese hamster cells. Biophys. J. 11, 502–520(1971).PubMedCrossRefGoogle Scholar
  15. Elkind, M.M., Sutton, H.: X-ray damage and recovery in mammalian cells in culture. Nature (Lond.) 184, 1293–1295 (1959).CrossRefGoogle Scholar
  16. Elkind, M.M., Whitmore, G.F.: The radiobiology of cultured mammalian cells. New York: Gordon and Breach 1967.Google Scholar
  17. Epstein, H.T.: Identification of radiosensitive volume with nucleic acid volume. Nature (Lond.) 171, 394–395 (1953).CrossRefGoogle Scholar
  18. Froese, G.: Division delay in Hela cells and Chinese hamster cells. A time-lapse study. Int. J. Radiat. Biol. 10, 353–367 (1966).CrossRefGoogle Scholar
  19. Goldstein, R., Okada, S.: Interphase death of cultured mammalian cells (L5178Y). Radiat. Res. 39, 361–373 (1969).PubMedCrossRefGoogle Scholar
  20. Hahn, G.M.: Radiobiology of mammalian cells in the plateau phase of growth. In: Time and dose relationships in radiation biology as applied to radiotherapy, pp. 117–125. Upton, N. Y.: Brookhaven National Laboratory 1970.Google Scholar
  21. Hewitt, H.B.: Studies on the dissemination and quantitative transplantation of a lymphocytic leukemia of CBA mice. Brit. J. Cancer 12, 378–401 (1958).PubMedCrossRefGoogle Scholar
  22. Hewitt, H.B., Wilson, C. W.: A survival curve for mammalian cells irradiated in vivo. Nature (Lond.) 183, 1060–1061 (1959).CrossRefGoogle Scholar
  23. Hewitt, H.B., Wilson, C.W.: Survival curves for tumor cells irradiated in vivo. Ann. N. Y. Acad. Sci. 95, 818–827 (1961).PubMedCrossRefGoogle Scholar
  24. Hopwood, L.E.: Ph. D. Thesis, Washington University, St. Louis, Mo. 1971.Google Scholar
  25. Hopwood, L.E., Tolmach, L.J.: Deficient DNA synthesis and mitotic death in x-irradiated Hela cells. Radiat. Res. 46, 70–84 (1971).PubMedCrossRefGoogle Scholar
  26. Hurwitz, C., Tolmach, L.J.: Time-lapse cinemicrographic studies of x-irradiated Hela S3 cells. I. Cell progression and cell disintegration. Biophys. J. 9, 607–633 (1969a).PubMedCrossRefGoogle Scholar
  27. Hurwitz, C., Tolmach, L.J.: Time-lapse cinemicrographic studies of x-irradiated Hela S3 cells. II. Cell fusion. Biophys. J. 9, 1131–1143 (1969 b).PubMedCrossRefGoogle Scholar
  28. Hutchinson, F.: Molecular basis for action of ionizing radiations. Science 134, 533–538 (1961).PubMedCrossRefGoogle Scholar
  29. Kaplan, H.S.: Radiobiology’s contribution to radiotherapy: Promise or mirage? Radiat. Res. 43, 460–476 (1970).PubMedCrossRefGoogle Scholar
  30. Kaplan, H.S., Moses, L.E.: Biological complexity and radiosensitivity. Science 145, 21–25 (1964).PubMedCrossRefGoogle Scholar
  31. Lajtha, L.G., Oliver, R., Kumatori, T., Ellis, F.: On the mechanism of radiation effect on DNA synthesis. Radiat. Res. 8, 1–16 (1958).PubMedCrossRefGoogle Scholar
  32. Lea, D.E.: Actions of radiations on living cells, 2nd ed. Cambridge: University Press 1955.Google Scholar
  33. Leeper, D.B., Sgkneiderman, M.H., Dewey, W.C.: Radiation induced cycle delay in synchronized Chinese hamster cells: Comparison between DNA synthesis and division. Radiat. Res. 53, 326–337 (1973).PubMedCrossRefGoogle Scholar
  34. Levis, A.G.: Effetti dei raggi x sulla mitosi di cellule di mammiferi coltivate in vitro. Caryologia 15, 59–87 (1962).Google Scholar
  35. Little, J.B.: Differential response of rapidly and slowly proliferating human cells to x-irradiation. Radiology 93, 307–313 (1969).PubMedGoogle Scholar
  36. Mcculloch, E.A., Till, J.E.: The radiation sensitivity of normal mouse bone marrow cells, determined by quantitative marrow transplantation into irradiated mice. Radiat. Res. 13, 115–125 (1960).PubMedCrossRefGoogle Scholar
  37. McCulloch, E.A., Till, J.E.: The sensitivity of cells from normal mouse bone marrow to gamma radiation in vitro and in vivo. Radiat. Res. 16, 822–832 (1962).PubMedCrossRefGoogle Scholar
  38. Madoc-Jones, H., Dawson, K.B., Field, E.O.: Radiosensitivity of a series of cultured primary fibrosarcomata. Radiology 90, 541–546 (1968).PubMedGoogle Scholar
  39. Madoc-Jones, H., Mauro, F.: Age response to x-rays, Vinca alkaloids, and hydroxyurea of murine lymphoma cells synchronized in vivo. J. nat. Cancer Inst. 45, 1131–1143 (1970).PubMedGoogle Scholar
  40. Marin, G., Bender, M. A.: A comparison of mammalian cell-killing by incorporated 3H-uridine. Int. J. Radiat. Biol. 7, 235–244 (1963).CrossRefGoogle Scholar
  41. Marin, G., Bender, M.A.: Radiation-induced mammalian cell death: lapse-time cinemicrographic observations. Exp. Cell Res. 43, 413–423 (1966).PubMedCrossRefGoogle Scholar
  42. Mauro, F., Madoc-Jones, H.: Age response to x-radiation of murine lymphoma cells synchronized in vivo. Proc. nat. Acad. Sci. (Wash.) 63, 686–689 (1969).CrossRefGoogle Scholar
  43. Mauro, F., Madoc-Jones, H.: Age response of cultured mammalian cells to cytotoxic drugs. Cancer Res. 30, 1397–1407 (1970).PubMedGoogle Scholar
  44. Munro, T.R.: Alpha irradiation of parts of single cells in tissue culture. Exp. Cell Res. 18, 76–99 (1959).PubMedCrossRefGoogle Scholar
  45. Okada, S.: Radiation biochemistry, Vol. 1. New York: Academic 1970.Google Scholar
  46. Painter, R.B.: The direct effect of x-irradiation on Hela S3 deoxyribonucleic acid synthesis. Radiat. Res. 16, 846–859 (1962).PubMedCrossRefGoogle Scholar
  47. Parker, L., Skarsgard, L.D., Emmerson, P.T.: Sensitization of anoxic mammalian cells to x-rays by triacetoneamine N-oxyl. Survival and toxicity studies. Radiat. Res. 38, 493–500 (1969).PubMedCrossRefGoogle Scholar
  48. Phillips, R.A., Tolmach, L.J.: Repair of potentially lethal damage in x-irradiated Hela cells. Radiat. Res. 29, 413–432 (1966).PubMedCrossRefGoogle Scholar
  49. Philpott, G.W., Shaeffer, C.W., Tolmach, L.J.: Reproductive survival of chick embryo cells irradiated in ovo and in vitro. Radiat. Res. 17, 508–518 (1962).PubMedCrossRefGoogle Scholar
  50. Powers, W.E., Tolmach, L.J.: A multicomponent x-ray survival curve for mouse lymphoma cells irradiated in vivo. Nature (Lond.) 197, 710–711 (1963).CrossRefGoogle Scholar
  51. Powers, W.E., Tolmach, L.J.: Demonstration of an anoxic component in a mouse tumor cell population by an in vivo assay of survival following irradiation. Radiology 83, 328–336 (1964).PubMedGoogle Scholar
  52. Powers, W.E., Palmer, L.A., Tolmach, L.J.: Cellular radiosensitivity and tumor curability. Nat. Cancer Inst. Monogr. 24, 169–185 (1967).PubMedGoogle Scholar
  53. Puck, T.T.: Quantitative studies of mammalian cells in vitro. Rev. mod. Phys. 31, 433–448 (1959).CrossRefGoogle Scholar
  54. Puck, T.T.: Cellular aspects of the mammalian radiation syndrome. Radiat. Res. 27, 272–283 (1966).CrossRefGoogle Scholar
  55. Puck, T.T., Marcus, P.I.: A rapid method for viable cell titration and clone production with Hela cells in tissue culture. Proc. nat. Acad. Sci. (Wash.) 41, 432–437 (1955).CrossRefGoogle Scholar
  56. Puck, T.T., Marcus, P.I.: Action of x-rays on mammalian cells. J. exp. Med. 103, 653–666 (1956).PubMedCrossRefGoogle Scholar
  57. Puck, T.T., Marcus, P.L., Cieciura, S. J.: Clonal growth of mammalian cells in vitro. J. exp. Med. 103, 273–284 (1956).PubMedCrossRefGoogle Scholar
  58. Puck, T.T., Steffen, J.: Life cycle analysis of mammalian cells. Biophys. J. 3, 379–397 (1963).PubMedCrossRefGoogle Scholar
  59. Rauth, A.M., Simpson, L.A.: The energy loss of electrons in solids. Radiat. Res. 22, 643–661 (1964).CrossRefGoogle Scholar
  60. Reinhold, H.S.: Quantitative evaluation of the radiosensitivity of cells of a transplantable rhabdomyosarcoma in the rat. Europ. J. Cancer 2, 33–42 (1966).CrossRefGoogle Scholar
  61. Révész, L., Littbrand, B.: Variation of the relative sensitivity of closely related neoplastic cell lines irradiated in culture in the presence or absence of oxygen. Nature (Lond.) 203, 742–744 (1964).CrossRefGoogle Scholar
  62. Silini, G., Hornsey, S.: Studies on cell-survival of irradiated Ehrlich ascites tumour. I. The effect of the host’s age and the presence of nonviable cells on tumour takes. Int. J. Radiat. Biol. 4, 127–134 (1961).PubMedCrossRefGoogle Scholar
  63. Silini, G., Hornsby, S.: Studies on cell-survival of irradiated Ehrlich ascites tumour. III. A comparison of the x-ray survival curves obtained with a diploid and a tetraploid strain. Int. J. Radiat. Biol. 5, 147–153 (1962).PubMedCrossRefGoogle Scholar
  64. Sinclair, W.K.: Cyclic x-ray responses in mammalian cells in vitro. Radiat. Res. 33, 620–643 (1968).PubMedCrossRefGoogle Scholar
  65. Skipper, H.E.: The cell cycle and chemotherapy of cancer. In: Baserga, R. (Ed.): The cell cycle and cancer, pp. 358–387. New York: Dekker 1971.Google Scholar
  66. Sparrow, A.H., Underbrink, A.G., Sparrow, R.C.: Chromosomes and cellular radiosen-sitivity. Radiat. Res. 32, 915–945 (1967).PubMedCrossRefGoogle Scholar
  67. Steward, P.G., Hahn, G.M.: The application of age response functions to the optimization of treatment schedules. Cell Tissue Kinet. 4, 279–291 (1971).PubMedGoogle Scholar
  68. Terasima, T., Tolmach, L.J., Changes in x-ray sensitivity of Hela cells during the division cycle. Nature (Lond.) 190, 1210–1211 (1961).CrossRefGoogle Scholar
  69. Terasdia, T., Tolmach, L.J.: Variations in several responses of Hela cells to x-irradiation during the division cycle. Biophys. J. 3, 11–33 (1963).CrossRefGoogle Scholar
  70. Thompson, L.H., Surr, H.D.: Proliferation kinetics of x-irradiated mouse L cells studied with time-lapse photography. I. Experimental methods and data analysis. Int. J. Radiat. Biol. 13, 391–397 (1967).CrossRefGoogle Scholar
  71. Thompson, L.H., Suit, H.D.: Proliferation kinetics of x-irradiated mouse L cells studied with time-lapse photography. II. Int. J. Radiat. Biol. 15, 347–362 (1969).CrossRefGoogle Scholar
  72. Till, J.E.: Radiosensitivity and chromosome numbers in strain L mouse cells in tissue culture. Radiat. Res. 15, 400–409 (1961).PubMedCrossRefGoogle Scholar
  73. Tolmach, L.J.: Growth patterns in x-irradiated Hela cells. Ann. N. Y. Acad. Sci. 95, 743–757 (1961).PubMedCrossRefGoogle Scholar
  74. Trott, K.R., Hug, O.: Intraclonal recovery of division probability in pedigrees of single x-irradiated mammalian cells. Int. J. Radiat. Biol. 17, 483–486 (1970).CrossRefGoogle Scholar
  75. Tubiana, M.: The kinetics of tumor cell proliferation and radiotherapy. Brit. J. Radiol. 44, 325–347 (1971).PubMedCrossRefGoogle Scholar
  76. Walters, R.A., Petersen, D.P.: Radiosensitivity of mammalian cells. II.Radiation effects on macromolecular synthesis. Biophys. J. 8, 1487–1504 (1968).PubMedCrossRefGoogle Scholar
  77. Weiss, B.G.: Perturbations in precursor incorporation into DNA of x-irradiated Hela S3 cells. Radiat. Res. 48, 128–145 (1971).PubMedCrossRefGoogle Scholar
  78. Whitmore, G.F., Stanners, C.P., Till, J.E., Gulyas, S.: Nucleic acid synthesis and the division cycle in x-irradiated L-strain mouse cells. Biochim. biophys. Acta (Amst.) 47, 66–77 (1961).CrossRefGoogle Scholar
  79. Whitmore, G.F., Till, J.E.: Quantitation of cellular radiobiological responses. Ann. Rev. nuclear Sci. 14, 347–374 (1964).CrossRefGoogle Scholar
  80. Withers, H. R.: The dose-survival relationship for irradiation of epithelial cells of mouse skin. Brit. J. Radiol. 40, 187–194 (1967).PubMedCrossRefGoogle Scholar
  81. Withers, H.R.: Biological basis for high-LET radiotherapy. Radiol. 108, 131–137 (1973).Google Scholar
  82. Withers, H.R., Elkind, M.M.: Radiosensitivity and fractionation response of crypt cells of mouse jejunum. Radiat. Res. 38, 598–613 (1969).PubMedCrossRefGoogle Scholar
  83. Yamada, M., Puck, T.T.: Action of radiation on mammalian cells. Proc. Nat. Acad. Sci. (Wash.) 47, 1181–1191 (1961).CrossRefGoogle Scholar

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© Springer-Verlag Berlin · Heidelberg 1974

Authors and Affiliations

  • L. J. Tolmach
  • L. E. Hopwood

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