Role of Membrane Lipid Composition in Radiation- Induced Death of Mammalian Cells

  • A. W. T. Konings


There have been many speculations during the last 10 years concerning a possible role of membrane lipids in cellular radiation injury. This article addresses this question and discusses recent experiments related to this topic If lipids are involved in the mechanism of radiation-induced cell death, then the most probable molecular reactions underlying this effect are related to lipid peroxidation.

In the first part of this paper, it is shown that the naturally occurring polyunsaturated fatty acyl (PUFA) chains of phospholipids, arachidonic acid (20: 4), and docosahexanoic acid (22: 6) are the most radiosensitive lipid moieties and are damaged by peroxidative reactions. Protection by vitamin E is very efficient. In the second part, experiments are discussed in which mammalian cells in culture are modified so that more PUFA is present in the membrane phospholipids. Also the antioxidant status of the cells is manipulated. The effect of these membrane modifications on radiation-induced reproductive death is reported. The third part of this article is concerned with the role of membrane lipids and protective systems in radiation-induced interphase death.


Lipid Peroxidation Dose Rate Membrane Fatty Acid Trypan Blue Oxygen Enhancement Ratio 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cole, A. Radiation effects on DNA and membranes. In: “Radiation Research.” Reviews and Summaries, Proceedings of the Seventh International Congress of Radiation Research. J. J. Broerse, G. W. Barendsen, H. B. Kal, and A. J. van der Kogel, eds. Martinus Nijhof Publishers, Amsterdam, 1983, pp. 225–230.Google Scholar
  2. 2.
    Alper, T., ed. “Cellular Radiobiology.” Cambridge University Press, Cambridge/London, 1979.Google Scholar
  3. 3.
    Okada, S. Radiation-induced death. In: “Radiation Biochemistry,” Vol. I. K. Z. Altman, G. B. Gerber, and S. Okada, eds. Academic Press, New York/ London, 1970, pp. 247–260.Google Scholar
  4. 4.
    Butler, J., Land, E. J., and Swallow, A. J. Chemical mechanisms of the effects of high energy radiation on biological systems. Radiat. Phys. Chem. 24: 273–282, 1984.CrossRefGoogle Scholar
  5. 5.
    Konings, A. W. T., Damen, J., and Trieling, W. B. Protection of liposomal lipids against radiation-induced oxidative damage. Int. J. Radiat. Biol. 35: 343–350, 1979.CrossRefGoogle Scholar
  6. 6.
    Mooibroek, J., Trieling, W. B., and Konings, A. W. T. Comparison of the radiosensitivity of unsaturated fatty acids, structured as micelles or liposomes, under different experimental conditions. Int. J. Radiat. Biol. 42: 601–609, 1982.CrossRefGoogle Scholar
  7. 7.
    Konings, A. W. T. Radiation protection of membranes by α-tocopherol. Int. J. Radiat. Biol. 38: 119, 1980.Google Scholar
  8. 8.
    Konings, A. W. T. Lipid peroxidation in liposomes. Preparation of liposomes. In: “Liposome Technology,” Vol. I. G. Gregoriades, ed. CRC Press, London/ New York, 1984, pp. 139–162.Google Scholar
  9. 9.
    Raleigh, J. A., and Kremers, W. Promotion of radiation peroxidation in models of lipid membranes by caesium and rubidium counter ions: Micellar linoleic and linolenic acids. Int. J. Radiat. Biol. 34: 439–447, 1978.CrossRefGoogle Scholar
  10. 10.
    Raleigh, J. A., Kremers, W., and Gaboury, B. Dose-rate and oxygen effects in models of lipid membranes: Linoleic acid. Int. J. Radiat. Biol. 31: 203–213, 1977.CrossRefGoogle Scholar
  11. 11.
    Konings, A. W. T. Radiation-induced efflux of potassium ions and haemoglobin in bovine erythrocytes at low doses and low dose-rates. Int. J. Radiat. Biol. 40: 441–444, 1981.CrossRefGoogle Scholar
  12. 12.
    Konings, A. W. T. Dose-rate effects on lymphocyte survival. J. Radiat. Res. 22: 282–285, 1981.PubMedCrossRefGoogle Scholar
  13. 13.
    Konings, A. W. T. Role of biologically available antioxidant compounds in the regulation of cellular radiosensitivity. In: “Oxygen and Sulfur Radicals in Chemistry and Medicine.” A. Breccia, M. A. J. Rodgers, and G. Semerano, eds. Edizioni Scientifiche “Lo Scarabeo”, Bologna, 1986, pp. 257–269.Google Scholar
  14. 14.
    Wolters, H., and Konings, A. W. T. Radiation effects on membranes. III. The effect of X-irradiation on survival of mammalian cells substituted by polyunsaturated fatty acids. Radiat. Res. 92: 474–482, 1982.Google Scholar
  15. 15.
    Wolters, H., Kelholt, D., and Konings, A. W. T. Effect of membrane fatty acid substitution and temperature on repair of sublethal damage in mammalian cells. Radiat. Res. 102: 206–212, 1985.PubMedCrossRefGoogle Scholar
  16. 16.
    George, A. M., Lunec, J., and Cramp, W. A. Effect of membrane fatty acid changes on the radiation sensitivity of human lymphoid cells. Int. J. Radiat. Biol. 43: 363–378, 1983.CrossRefGoogle Scholar
  17. 17.
    Goulet, D. L., Fisher, G. J., Pageau, R., and Van Lier, J. E. Effect of membrane fatty acid composition on radiosensitivity of V79 Chinese hamster cells. Biochim. Biophys. Acta 875: 414–417, 1986.PubMedGoogle Scholar
  18. 18.
    Konings, A. W. T. Mechanisms of ozone toxicity in cultured cells. I. Reduced clonogenic ability of polyunsaturated fatty acid-supplemented fibroblasts. Effect of vitamin E. J. Toxicol. Environ. Health 18: 491–497, 1986.Google Scholar
  19. 19.
    Wolters, H., and Konings, A. W. T. Radiosensitivity of normal and polyunsaturated fatty acid supplemented fibroblasts after depletion of glutathione. Int. J. Radiat. Biol. 46: 161–168, 1984.CrossRefGoogle Scholar
  20. 20.
    Wolters, H., Van Tilburg, C. A. M., and Konings, A. W. T. Radiation induced lipid peroxidation: Influence of oxygen concentration and membrane lipid composition. Int. J. Radiat. Biol. 51: 619–629, 1987.CrossRefGoogle Scholar
  21. 21.
    Konings, A. W. T., and Ruifrok, A. C. C. Role of membrane lipids and membrane fluidity in thermosensitivity and thermotolerance of mammalian cells. Radiat. Res. 102: 86–98, 1985.PubMedCrossRefGoogle Scholar
  22. 22.
    Raaphorst, G. P., Vadasz, J. A., and Azzam, E. I. Thermal sensitivity and radiosensitization in V79 cells after BrdUrd or IdUrd incorporation. Radiat. Res. 98: 167–175, 1984.PubMedCrossRefGoogle Scholar
  23. 23.
    Konings, A. W. T. The involvement of polyunsaturated fatty acyl chains of membrane phospholipids in radiation-induced cell death of mammalian cells. In: “Oxygen Radicals in Chemistry and Biology.” W. Bors, M. Saran, and D. Tait, eds. Walter de Gruyter & Co., Berlin/New York, 1984, pp. 593–602.CrossRefGoogle Scholar
  24. 24.
    Wolters, H., and Konings, A. W. T. Membrane radiosensitivity of fatty acid supplemented fibroblasts as assayed by the loss of intracellular potassium. Int. J. Radiat. Biol. 48: 963–973, 1985.CrossRefGoogle Scholar
  25. 25.
    Fonck, K., Scherphof, G. L., and Konings, A. W. T. Control of fatty acid incorporation in membrane phospholipids; X-ray-induced changes in fatty acid uptake by tumor cells. Biochim. Biophys. Acta 692: 406–414, 1982.PubMedCrossRefGoogle Scholar
  26. 26.
    Fonck, K., Scherphof, G. L., and Konings, A. W. T. The effect of X-irradiation on membrane lipids of lymphosarcoma cells in vivo and in vitro. J. Radiat. Res. 23: 371–384, 1982.PubMedCrossRefGoogle Scholar
  27. 27.
    Konings, A. W. T., and Drijver, E. B. Radiation effects on membranes. I. Vitamin E deficiency and lipid peroxidation. Radiat. Res. 80: 494, 1979.Google Scholar
  28. 28.
    Malick, M. A., Roy, R. M., and Sternberg, J. Effect of vitamin E on post-irradiation death in mice. Experientia 34: 1216, 1978.PubMedCrossRefGoogle Scholar
  29. 29.
    Sakamoto K., and Sakka, M. Reduced effect of irradiation on normal and malignant cells irradiated in vivo in mice pretreated with vitamin E. Brit. J. Radiol. 46: 538, 1973.PubMedCrossRefGoogle Scholar
  30. 30.
    Srinivasan, V., and Weiss, J. F. Vitamins and radiation injury: Vitamin E, vitamin B6, and liver microsomal drug-metabolizing system. Radiat. Res. 87: 385, 1981.Google Scholar
  31. 31.
    Bichay, T. J. E., and Roy, R. M. Modification of survival and hematopoiesis in mice by tocopherol injection following irradiation. Strahlenther. & Onkologie 162: 391–399, 1986.Google Scholar
  32. 32.
    Ojeda, F., Moraga, D., Guarda, M. I., and Folch, H. Dose rate dependence of radiation induced IgG membrane receptor alteration. Z. Naturforsch. 39c: 1021–1022, 1984.Google Scholar
  33. 33.
    Koteles, G. J., Kubasova, T., Somosy, Z., and Horvath, L. Derangement of cellular plasma membranes due to non-lethal radiation doses. In: “Biological Effects of Low-level Radiation.” IAEA-SM-266/37. International Atomic Energy Agency, Vienna, 1983, pp. 115–128.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • A. W. T. Konings
    • 1
  1. 1.Department of RadiopathologyUniversity of GroningenGroningenThe Netherlands

Personalised recommendations