A Method to Measure the Radio and Chemosensitivity of Human Spheroids

  • J. Carlsson
  • T. Nederman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 159)


A method based on the spontanous outgrowth of cells from spheroids was tested. Different outgrowth patterns were seen depending on the types of spheroids and on the radiation or drug doses. The method allowed dose-effect relations to be determined. Spheroid survival was defined as when the outgrowing monolayers contained at least thousand cells within five weeks. The method was used as an alternative to cloning of isolated single cells. The gliana and osteosarcoma spheroids could not be disintegrated to single cell suspensions since they resisted enzymatic and mechanical treatments for cell separation. Detection of differences in radio and chemosensitivity between different types of spheroids of human origin might be valuable for the understanding of the large variations in therapeutical response often seen between different types of tumors.


Radial Outgrowth Outgrowth Test Spheroid Cell Spontanous Outgrowth Spheroid Culture 
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  1. Alper, T., Cellular Radiobiology, Cambridge University Press, Cambridge, 1979.Google Scholar
  2. Altman, K. I., Gerber, G. B. and Okada, S. Radiation Bio-chemistry. Vol. I. Academic Press, New York and London pages 239–246, 1970.Google Scholar
  3. Carlsson, J., Lundqvist, H. and Pontén, J. The measurement of spatial precursor distributions in cell culture. In Vitro, 12, 571–579, 1976.Google Scholar
  4. Carlsson, J. A proliferation Gradient in Three-Dimensional Colonies of Cultured Human Glioma Cells. Int. J. Cancer 20, 129–136, 1977.Google Scholar
  5. Carlsson, J. and Brunk, U. The Fine Structure of Three-Dimensional Colonies of Human Glioma Cells in Agarose Culture. Acta Path. Microbial. Scand. Sect. A, 85, 183–192, 1977.Google Scholar
  6. Carlsson, J., Collins, P. and Brunk, U. Plasma membrane motility and proliferation of human gliama cells in agarose and monolayer cultures. Acta path. microbial. Scand. Sect. A, 86, 45–55, 1978.Google Scholar
  7. Carlsson, J. Physical and nutritional factors in gel culture of mammalian cells. In Vitro, 14, 860–867, 1978.Google Scholar
  8. Carlsson, J., Stalnacke, C. G., Acker H., Haji-Karim, M.Google Scholar
  9. Nilsson, S. and Larsson, B. The influence of oxygen on viability and proliferation in cellular spheroids. Int. J. Rad. Onc. Biol. Phys., 5, 2011–2020, 1979.CrossRefGoogle Scholar
  10. Denekamp, J. The relationship between cell loss factor and the immediate response to radiation in animal tumours. Eur. J. Canrer, 8, 335–340, 1972.CrossRefGoogle Scholar
  11. Durand, R. E. Cure, regression and cell survival: a comparison of canon radiobiological endpoints using an in vitro tumour model. Brit. J. Cancer 48, 556–571, 1975.Google Scholar
  12. Fowler, J. A. Animal experiments required for radiobiology applied to radiotherapy. Radiobiological Research and Radiotherapy. Proceedings of a symposium. Vienna, IAEA, Vienna, 1977.Google Scholar
  13. Freyer, J. P. and Sutherland, R. M. Selective dissociation and characterization of cells from different regions of multicell tumour spheroids. Cancer Res., 40, 3956–3965, 1980.PubMedGoogle Scholar
  14. Sutherland, R. M., McX redie, J. A. and Inch, W. R. Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. J. Nat. Cancer Inst., 46, 113–120, 1971.Google Scholar
  15. Sutherland, R. M. and Durand, R. E. Radiation Response of Multicell Spheroids. An In Vitro Tumour Model. Current Topics in Rad. Res. Qlartely Vol. 11, No. 1, 87–139, 1976.Google Scholar
  16. Westermark, B. The deficient densitydependent growth control of human malignant gliana cells and virus transformed glia-like cells in culture. Int. J. Cancer, 12, 438–451, 1973.PubMedCrossRefGoogle Scholar
  17. Whiters, H. R. Biological basis for high-LET radiotherapy. Radiology, 108, 131–137, 1973.Google Scholar
  18. Whiters, H. R. and Suit, H. Is oxygenation important of theGoogle Scholar
  19. radiocurability of human tumours? The biological and clinical basis of radiosensitivity (Ed. Friedman, M.) C. C. Thanas publisher, Springfield, p. 548–560, 1974.Google Scholar
  20. Yuhas, J. M., Li, A. P., Martinez, A. O. and Ladman, A. J.A simplified method for production and growth of multi-cellular tumour spheroids. Cancer Research, 37, 3639–3643, 1977.PubMedGoogle Scholar
  21. Haji-Karim, M. and Carlsson, J. Proliferation and viability in cellular spheroids of human origin. Cancer Research 38, 1457–1464, 1978.PubMedGoogle Scholar
  22. Nilsson, S., Carlsson, J., Larsson, B. and Pontdn, J. Survival of irradiated glia and gliana cells studied with a new cloning technique. Int. J. Radiat. Biol., 37, 267–279, 1980.CrossRefGoogle Scholar
  23. Ponten, J. and Saksela, E. Two established in vitro cell lines from human mesenchymal tumours. Int. J. Cancer 2, 434447, 1967.Google Scholar
  24. Ponten, J. and Macintyre, E. H. Long term culture of normal and neoplastic human glia. Acta Pathol. Microbial. Scand. 74, 465–486, 1968.CrossRefGoogle Scholar
  25. Puck, T. T. and Marcus, P. I. Action of X-rays on mammalian cells. J. Exp. Med. 103, 653–666, 1956.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • J. Carlsson
    • 1
    • 2
    • 3
  • T. Nederman
    • 1
    • 2
    • 3
  1. 1.Dept. of RadiobiologyNational Defense Research InstituteUmeaSweden
  2. 2.Dept. of Physical BiologyGustaf Werner InstituteUmeaSweden
  3. 3.UppsalaSweden

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