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

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

Abstract

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.

Keywords

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.

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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

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