Radiation Peroxidation in Model Membranes

  • J. A. Raleigh


The potential for chain reaction decomposition puts unsaturated lipids among the most radiosensitive of biological molecules. The possibility that radiation peroxidation of unsaturated lipids in biological membranes might underlie some of the biological effects of ionizing radiation has prompted a number of studies of radiation-induced lipid peroxidation. In model membranes the hydroxyl radical (OH) from water radiolysis initiates peroxidation which proceeds without a lag phase. The process is dose-rate dependent, with peroxidation increasing with decreasing dose rate. In spite of the fact that OH initiates peroxidation, not all OH scavengers inhibit peroxidation. Secondary peroxy radicals from the OH scavengers might in some cases (e.g., dimethylsulfoxide, DMSO) initiate peroxidation as efficiently as OH radicals. An additional important feature of radiation-induced lipid peroxidation is that approximately 60% of the peroxides formed in linoleic acid (18: 2) are diene-conjugated hydroperoxides, whereas in linolenic acid (18: 3) these are minor products even though overall oxygen consumptions are similar for the two unsaturated fatty acids. The difference in product distribution can be accounted for, in part, by the formation of malonaldehyde-type products in linolenic acid. The formation of these products is also subject to the paradoxical effect of OH scavengers. Antioxidants such as vitamin E remove the paradoxical OH scavenger effect. Studies like these can be instructive in unravelling the effects of ionizing radiation on biological membranes. For example, we have concluded from these studies that the paradoxical effect of the OH scavenger dimethylsulfoxide on erythrocyte hemolysis arises in the lipid component of the plasma membrane and is due to secondary peroxy radicals formed from dimethylsulfoxide. The effect appears to occur in the initial stages of radiation damage and precedes the extensive autoxidative degradation of membrane lipids that parallels hemolysis during the postirradiation incubation period.


High Performance Liquid Chromatography Unsaturated Fatty Acid Critical Micelle Concentration Mixed Micelle Lipid Hydroperoxide 
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.
    Myers, D. K., and Bide, R. W. Biochemical effects of X-irradiation on erythrocytes. Radiat. Res. 27: 250–263, 1966.CrossRefGoogle Scholar
  2. 2.
    Wills, E. D., and Wilkinson, A. E. The effect of irradiation on lipid peroxide formation in subcellular fractions. Radiat. Res. 31: 732–747, 1967.CrossRefGoogle Scholar
  3. 3.
    Wills, E. D. Effects of irradiation on subcellular components. I. Lipid peroxide formation in the endoplasmic reticulum. Int. J. Radiat. Biol. 17: 217–228, 1970.CrossRefGoogle Scholar
  4. 4.
    Konings, A. W. T., and Oosterloo, S. K. Radiation effects on membranes. II. A comparison of the effects of X-irradiation and ozone exposure with respect to the relation of antioxidant concentration and the capacity for lipid peroxidation. Radiat. Res. 81: 200–207, 1980.PubMedCrossRefGoogle Scholar
  5. 5.
    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
  6. 6.
    Lands, W. E. M. Interactions of lipid hydroperoxides with eicosanoid biosynthesis. J. Free Rad. Biol. Med. 1: 97–101, 1985.CrossRefGoogle Scholar
  7. 7.
    Marshall, P. J., Kulmacz, R. J., and Lands, W. E. M. Hydroperoxides, free radicals, and prostaglandin synthesis. In: “Oxygen Radicals in Chemistry and Biology.” W. Bors, M. Saran, and D. Tait, eds. de Gruyter, New York, 1984, pp. 299–307.CrossRefGoogle Scholar
  8. 8.
    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. de Gruyter, New York, 1984, pp. 593–602.CrossRefGoogle Scholar
  9. 9.
    Frankel, E. N. Chemistry of free radical and singlet oxidation of lipids. Prog. Lipid Res. 23: 197–221, 1985.CrossRefGoogle Scholar
  10. 10.
    Petkau, A., and Chelak, W. S. Radioprotective effect of superoxide dismutase on model phospholipid membranes. Biochim. Biophys. Acta 433: 445–456, 1976.PubMedCrossRefGoogle Scholar
  11. 11.
    Nakazawa, T., and Nagatsuka, S. Radiation-induced lipid peroxidation and membrane permeability in liposomes. Int. J. Radiat. Biol. 38: 537–544, 1980.CrossRefGoogle Scholar
  12. 12.
    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
  13. 13.
    Anbar, M., and Neta, P. A compilation of specific bimolecular rate constants for the reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals with inorganic and organic compounds in aqueous solutions. Int. J. Appl. Rad. Isotop. 18: 493–523, 1967.CrossRefGoogle Scholar
  14. 14.
    Behar, D., Czapski, G., Robani, J., Dorfman, L. M., and Schwarz, H. A. The acid dissociation constant and decay kinetics of the perhydroxyl radical. J. Phys. Chem. 74: 3209–3213, 1970.CrossRefGoogle Scholar
  15. 15.
    Patterson, L. K., and Redpath, J. L. Radiation-induced peroxidation in fatty acid soap micelles. In: “Micellization, Solubilization and Microemulsions,” Vol. 2. K. L. Mittal, ed. Plenum Press, New York, 1977, pp. 589–601.CrossRefGoogle Scholar
  16. 16.
    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
  17. 17.
    Gebicki, J. M., and Bielski, B. H. J. Comparison of the capacities of the perhydroxyl and the superoxide radicals to initiate chain oxidation of linoleic acid. J. Amer. Chem. Soc. 103: 7020–7023, 1981.CrossRefGoogle Scholar
  18. 18.
    Bielski, B. H., Arudi, R. L., and Sutherland, M. W. A study of the reactivity of HO2/O2−˙ with unsaturated fatty acids. J. Biol. Chem. 258: 4759–4761, 1983.PubMedGoogle Scholar
  19. 19.
    Thomas, M. J., Sutherland, M. W., Arudi, R. L., and Bielski, B. H. J. Studies of the reactivity of HO2/O2−˙ with unsaturated hydroperoxides in ethanolic solutions. Arch. Biochem. Biophys. 233: 772–775, 1984.PubMedCrossRefGoogle Scholar
  20. 20.
    Girotti, A. W. Mechanisms of lipid peroxidation. J. Free Rad. Biol. Med. 1: 87–95, 1985.CrossRefGoogle Scholar
  21. 21.
    Small, R. D., Jr., Scaiano, J. C., and Patterson, L. K. Radical processes in lipids. A laser photolysis study of t-butoxy radical reactivity toward fatty acids. Photochem. Photobiol. 29: 49–51, 1979.Google Scholar
  22. 22.
    Bascetta, E., Gunstone, F. D., Scrimgeour, C. M., and Walton, J. C. E.S.R. observation of pentadienyl and allyl radicals on hydrogen abstraction from unsaturated lipids. J. Chem. Soc, Chem. Commun. 110–112, 1982.Google Scholar
  23. 23.
    Fukuzawa, K., and Gebicki, J. M. Oxidation of α-tocopherol in micelles and liposomes by the hydroxyl, perhydroxyl, and superoxide free radicals. Arch. Biochem. Biophys. 226: 242–251, 1983.PubMedCrossRefGoogle Scholar
  24. 24.
    Raleigh, J. A., and Shum, F. Y. Radioprotection in model lipid membranes by hydroxyl radical scavengers: Supplementary role for α-tocopherol in scavenging secondary peroxy radicals. In: “Radioprotectors and Anticarcinogens.” O. F. Nygaard and M. G. Simic, eds. Academic Press, New York, 1983, pp. 87–102.Google Scholar
  25. 25.
    Patterson, L. K., and Hasegawa, K. Pulse radiolysis studies in model lipid systems. The influence of aggregation on kinetic behavior of OH induced radicals in aqueous sodium linoleate. Ber. Bunsenges. Phys. Chem. 82: 951–956, 1978.Google Scholar
  26. 26.
    Heijman, M. G. J., Nauta, H., and Levine, Y. K. A pulse radiolysis study of the dienyl radical in oxygen-free linoleate solutions: Time and linoleate concentration dependence. Radiat. Phys. Chem. 26: 73–82, 1985.CrossRefGoogle Scholar
  27. 27.
    Heijman, M. G. J., Heitzman, A. J. P., Nauta, H., and Levine, Y. K. A pulse radiolysis study of the reactions of OH/O− with linoleic acid in oxygen-free aqueous solution. Radiat. Phys. Chem. 26: 83–88, 1985.CrossRefGoogle Scholar
  28. 28.
    Patterson, L. K. Studies of radiation induced peroxidation in fatty acid micelles. In: “Oxygen and Oxy-Radicals in Chemistry and Biology.” M. A. J. Rodgers and E. L. Powers, eds. Academic Press, New York, 1981, pp. 89–95.Google Scholar
  29. 29.
    Howton, D. R. Nature of the products formed by gamma irradiation of deaerated aqueous potassium oleate. Radiat. Res. 20: 161–186, 1963.CrossRefGoogle Scholar
  30. 30.
    Patterson, L. K. Investigation of micellar behavior by pulse radiolysis. In: “Solution Behavior of Surfactants,” Vol. 1. K. L. Mittal and E. J. Fendler, eds. Plenum Press, New York, 1982, pp. 285–297.CrossRefGoogle Scholar
  31. 31.
    Korcek, S., Chenier, J. H. B., Howard, J. A., and Ingold, K. U. Absolute rate constants for hydrocarbon autoxidation. XXI. Activation energies for propagation and the correlation of propagation rate constants with carbon-hydrogen bond strengths. Can. J. Chem. 50: 2285–2297, 1972.Google Scholar
  32. 32.
    Mandai, T. K., and Chatterjee, S. N. Ultraviolet and sunlight-induced lipid peroxidation in liposomal membrane. Radiat. Res. 83: 290–302, 1980.CrossRefGoogle Scholar
  33. 33.
    Gebicki, J. M., and Allen, A. O. Relationship between critical micelle concentration and rate of radiolysis of aqueous sodium linoleate, J. Phys. Chem. 73: 2443–2445, 1969.CrossRefGoogle Scholar
  34. 34.
    Raleigh, J. A., and Kremers, W. Promotion of radiation peroxidation in models of lipid membrane by cesium and rubidium counter-ions: Micellar linoleic and linolenic acids. Int. J. Radiat. Biol. 34: 439–447, 1978.CrossRefGoogle Scholar
  35. 36.
    Eriksson, J. C., and Gillberg, G. NMR-studies of the solubilization of aromatic compounds in cetyltrimethylammonium bromide solution. Surface Chemistry 148–156, 1965.Google Scholar
  36. 37.
    Mead, J. F. The irradiation-induced autoxidation of linoleic acid. Science 115: 470–472, 1952.PubMedCrossRefGoogle Scholar
  37. 38.
    Petkau, A. Effect of 22Na+ on a phospholipid membrane. Health Physics 22: 239–244, 1972.PubMedCrossRefGoogle Scholar
  38. 39.
    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
  39. 40.
    Chatterjee, S. N., and Agarwal, S. Lipid peroxidation by ultraviolet light and high energy α particles from a cyclotron. Radiat. Environ. Biophys. 21: 275–280, 1983.PubMedCrossRefGoogle Scholar
  40. 41.
    Spinks, J. W. T., and Woods, R. J. In: “An Introduction to Radiation Chemistry,” second edition. Wiley-Interscience, New York, 1976, pp. 187–191.Google Scholar
  41. 42.
    Raleigh, J. A., and Kremers, W. DMSO does not protect against hydroxyl radical induced peroxidation in model membranes. Int. J. Radiat. Biol. 39: 441–444, 1981.CrossRefGoogle Scholar
  42. 43.
    Reuvers, A. P., Greenstock, C. L., Borsa, J., and Chapman, J. D. Studies on the mechanism of chemical radioprotection by dimethylsulfoxide. Int. J. Radiat. Biol. 24: 533–536, 1973.CrossRefGoogle Scholar
  43. 44.
    Mittal, K. L., and Mukerjee, P. The wide world of micelles. In: “Micellization, Solubilization, and Microemulsions,” Vol. 1. K. L. Mittal, ed. Plenum Press, New York, 1977, pp. 1–21.CrossRefGoogle Scholar
  44. 45.
    Chapman, D., Fluck, D. J., Penkett, S. A., and Shipley, G. G. Physical studies of phospholipids X. The effect of sonication of aqueous dispersions of egg yolk lecithin. Biochim. Biophys. Acta 163: 255–261, 1968.Google Scholar
  45. 46.
    Edwards, J. C., and Quinn, P. J. The structure of unsaturated lipid dispersions in aqueous systems influences susceptibility to oxidation. Biochim. Biophys. Acta 710: 502–505, 1982.PubMedGoogle Scholar
  46. 47.
    Goldstein, S., and Czapski, G. Mannitol as an OH scavenger in aqueous solution and in biological systems. Int. J. Radiat. Biol. 46: 725–729, 1984.CrossRefGoogle Scholar
  47. 48.
    Willson, R. L., Greenstock, C. L., Adams, G. E., Wageman, R., and Dorfman, L. M. The standardization of hydroxyl radical rate data from radiation chemistry. Int. J. Radiat. Phys. Chem. 3: 211–220, 1971.CrossRefGoogle Scholar
  48. 49.
    Raleigh, J. A., and Shum, F. Y. Radiation peroxidation in micellar fatty acids. In: “Oxygen Radicals in Chemistry and Biology.” W. Bors, M. Saran, and D. Tait, eds. de Gruyter, New York, 1984, pp. 581–591.CrossRefGoogle Scholar
  49. 50.
    Ross, A. B., and Neta, P. Rate constants for radiation of aliphatic carbon-centered radicals in aqueous solution. U.S. National Bureau of Standards (NSRDS-NBS 70), Gaithersburg, MD, 1982, pp. 25–27.Google Scholar
  50. 51.
    Bothe, E., Schuchman, M. N., Schulte-Frohlinde, D., and von Sonntag, C. HO2 elimination from α-hydroxyalkyl-peroxyl radicals in aqueous solutions. Photochem. Photobiol. 28: 639–644, 1978.CrossRefGoogle Scholar
  51. 52.
    Anbar, M., Meyerstein, D., and Neta, P. Reactivity of aliphatic compounds towards hydroxyl radicals. J. Chem. Soc. B: 742–747, 1966.Google Scholar
  52. 53.
    Pollster, B. H., and Mead, J. F. Effect of certain vitamins and antioxidants on irradiation-induced autoxidation of methyl linoleate. Agric. Food Chem. 2: 199–202, 1954.CrossRefGoogle Scholar
  53. 54.
    Howard, J. A., and Ingold, K. U. Absolute rate constants for hydrocarbon autoxidation. VI. Alkyl, aromatic, and olefinic hydrocarbons. Can. J. Chem. 45: 793–802, 1967.Google Scholar
  54. 55.
    Hunter, E. P. L., and Simic, M. G. Kinetics of peroxy radical reactions with antioxidants. In: “Oxy-Radicals and Their Scavenging Systems,” Vol. 1. G. R. A. Greenwald, eds. Elsevier, New York, 1983, pp. 32–37.Google Scholar
  55. 56.
    Burton, G. W., Doba, T., Gobe, E. J., Hughes, L., Lee, F. L., Prasad, L., and Ingold, K. U. Autoxidation of biological molecules. 4. Maximizing the antioxidant activity of phenols. J. Amer. Chem. Soc. 107: 7053–7065, 1985.Google Scholar
  56. 57.
    Gebicki, J. M. Linoleate micelles as models for radiobiological effects. In: “Biophysical Aspects of Radiation Quality.” International Atomic Energy Agency, Vienna, 1971, pp. 229–238.Google Scholar
  57. 58.
    Raleigh, J. A., Shum, F. Y., and Koch, C. J. Radiation chemistry of membrane damage. Distribution of oxygenated products in linoleate and linolenate micelles irradiated at low doses. Proc. 7th I.C.R. R., A4-31. Amsterdam, 1983.Google Scholar
  58. 59.
    Holman, R. T., and Elmer, D. C. The rates of oxidation of unsaturated fatty acids and esters. J. Amer. Oil Chem. Soc. 24: 127–129, 1947.CrossRefGoogle Scholar
  59. 60.
    Wong, W-S. D., and Hammond, E. G. Analysis of oleate and linoleate hydroperoxides in oxidized ester mixtures. Lipids 12: 475–479, 1977.CrossRefGoogle Scholar
  60. 61.
    Howard-Flanders, P., and Alper, T. The sensitivity of microorganisms to irradiation under controlled gas conditions. Radiat. Res. 7: 518–540, 1957.PubMedCrossRefGoogle Scholar
  61. 62.
    Koch, C. J. Competition between radiation protectors and radiation sensitizers in mammalian cells. In: “Radioprotectors and Anticarcinogens.” O. F. Nygaard and M. G. Simic, eds. Academic Press, New York, 1983, pp. 275–295.Google Scholar
  62. 63.
    Alper, T. “Cellular Radiobiology.” Cambridge University Press, New York, 1979.Google Scholar
  63. 64.
    Hall, E. J. “Radiobiology for the Radiologist,” second edition. Harper and Row, New York, 1978, pp. 148–150.Google Scholar
  64. 65.
    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
  65. 66.
    Edwards, J. C., Chapman, D., Cramp, W. A., and Yatvin, M. B. The effects of ionizing radiation on biomembrane structure and function. Prog. Biophys. Mol. Biol. 43: 71–93, 1984.PubMedCrossRefGoogle Scholar
  66. 67.
    Lal, M. Radiolytic oxidation of cysteine in aerated and oxygen saturated solution. Radiat. Phys. Chem. 19: 427–434, 1982.CrossRefGoogle Scholar
  67. 68.
    Robinson, J. D. Interaction between protein sulphydryl groups and lipid double bonds in biological membranes. Nature, Vol. 212(58): 199–200, 1966.PubMedCrossRefGoogle Scholar
  68. 69.
    Miller, G. G., and Raleigh, J. A. Action of some hydroxyl radical scavengers on radiation-induced haemolysis. Int. J. Radiat. Biol. 43: 411–419, 1983.CrossRefGoogle Scholar
  69. 70.
    Hatefi, Y., and Hanstein, W. G. Solubilization of particulate proteins and non-electrolytes by chaotropic agents. Proc. Natl. Acad. Sci. USA 62: 1129–1136, 1969.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • J. A. Raleigh
    • 1
  1. 1.Department of RadiobiologyCross Cancer InstituteEdmontonCanada

Personalised recommendations