The Role of Modification of DNA Damage in the Radioprotective Action of Aminothiols

  • David Murray
  • Susanna vanAnkeren
  • Luka Milas
  • Raymond Meyn


The role of DNA damage modification in the protection of mammalian cells from the lethal effects of radiation by aminothiols has been the subject of much research over the last 20 years since the early demonstrations that cysteamine reduced the level of DNA single-strand breaks (SSBs) in irradiated cells (1, 2). Despite this considerable effort, the actual mechanisms of radioprotection at both the cellular and DNA level remain poorly defined. Perhaps one barrier to our understanding of these effects has been the failure to recognize that many chemical modifiers of radiosensitivity, including sensitizers such as oxygen and protectors such as cysteamine, may not simply dose-modify numbers of DNA lesions but may also change the “spectrum” of lesions induced by low-LET radiations. For example, lesions such as DNA-protein cross-links (DPCs) (3) and 8,5’-cycloadenosine (4) are actually preferentially induced under hypoxia despite the fact that this condition offers considerable radioprotection to the cell. Even these presumably minor lesions could contribute significantly to lethality under appropriate conditions, e.g. in cells exhibiting a particular repair defect (3). Evidence that aminothiols also cause a shift in the spectrum of radiation-induced lesions comes from the recent report by Radfotd (5) that cysteamine altered the levels of 4 types of roiA lesion—SSBs, double-strand breaks (DSBs), DPCs and base damage—in different proportions.


Elution Method Minor Lesion Alkaline Elution RADIOPROTECTIVE Action Lethal Lesion 
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.
    P.H.M. Lohman, O. Vos, C.A. Van Sluis and J.A. Cohen. Chemical protection against breaks induced in DNA of human and bacterial cells by x-irradiation. Biochim. Biophys. Acta 224, 339–352 (1970).PubMedGoogle Scholar
  2. 2.
    S. Sawada and S. Okada, Cysteamine, cystamine, and single-strand breaks of DNA in cultured mammalian cells. Radiat. Res. 44, 116–132 (1970).PubMedCrossRefGoogle Scholar
  3. 3.
    R.E. Meyn, S.C. vanAnkeren, and W.T. Jenkins, The induction of DNA-protein crosslinks in hypoxic cells and their possible contribution to cell lethality. Radiat. Res. 109, 419–429 (1987).PubMedCrossRefGoogle Scholar
  4. 4.
    A.F. Fuciarelli, G.G. Miller, and J.A. Raleigh, An immunochemical probe for 8,5’-cycloadenosine-5’-monophosphate and its deoxy analog in irradiated nucleic acids. Radiat. Res. 104, 272–283 (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    I.R. Radford, Effect of radiomodifying agents on the ratios of X-ray-induced lesions in cellular DNA: use in lethal lesion determination. Int. J. Radiat. Biol. 49, 621–637 (1986).CrossRefGoogle Scholar
  6. 6.
    K.W. Kohn, R.A.G. Bvig, L.C. Erickson, and L.A. Zvelling, Measurement of strand breaks and cross-links by alkaline elution. In DNA Repair; A Laboratory Manual of Research Procedures (E. Friedberg and P. Hanavalt, Eds.), pp 379–402. Marcel Dekker, Inc., New York, 1981.Google Scholar
  7. 7.
    M.O. Bradley and K.W. Kohn, X-ray induced DNA double strand break production and repair in Baimalian cells as measured by neutral filter elution. Nucleic Acids Res. 7, 793–804 (1979).PubMedCrossRefGoogle Scholar
  8. 8.
    K.D. Held, G.D. Bren, and D.C. Melder, Interactions of radioprotectors and oxygen in cultured mammalian cells. II. Effects of dithiothreitol on radiation-induced DNA damage and comparison vith cell survival. Radiat. Res. 108, 296–306 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    D.J. Grdina and B. Nagy, The effect of 2-[(aminopropyl)amino] ethanethiol (VR-1065) on radiation-induced DNA damage and repair and cell progression in V79 cells. Br. J. Cancer 54, 933–941 (1986).PubMedCrossRefGoogle Scholar
  10. 10.
    P.E. Brown, Mechanism of action of aminothiol radioprotectors. Nature 363–364 (1967).Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • David Murray
    • 1
  • Susanna vanAnkeren
    • 1
  • Luka Milas
    • 1
  • Raymond Meyn
    • 1
  1. 1.M.D. Anderson Hospital and Tumor Institute Department of Experimental RadiotherapyThe University of Texas System Cancer CenterHoustonUSA

Personalised recommendations