1987 | OriginalPaper | Buchkapitel
The Role of Modification of DNA Damage in the Radioprotective Action of Aminothiols
verfasst von : David Murray, Susanna vanAnkeren, Luka Milas, Raymond Meyn
Erschienen in: Anticarcinogenesis and Radiation Protection
Verlag: Springer US
Enthalten in: Professional Book Archive
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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.