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环境病理学,毒理学和肿瘤学期刊
CiteScore™: 1.61 影响因子: 1.15 5年影响因子: 1.4 SNIP: 0.613 SJR: 0.519

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvPathToxOncol.v23.i1.30
12 pages

Radiation-Induced DNA Damage: Formation, Measurement, and Biochemical Features

Jean Cadet
Laboratoire "Lesions des Acides Nucleiques," SCIB/DRFMC, CEA/Grenoble, France
Sophie Bellon
Laboratoire "Lesions des Acides Nucleiques," SCIB/DRFMC, CEA/Grenoble, France
Thierry Douki
Laboratoire "Lesions des Acides Nucleiques," SCIB/DRFMC, CEA/Grenoble, France
Sandrine Frelon
Laboratoire "Lesions des Acides Nucleiques," SCIB/DRFMC, CEA/Grenoble, France
Didier Gasparutto
Laboratoire "Lesions des Acides Nucleiques," SCIB/DRFMC, CEA/Grenoble, France
Evelyne Muller
Laboratoire "Lesions des Acides Nucleiques," SCIB/DRFMC, CEA/Grenoble, France
Jean-Pierre Pouget
Laboratoire "Lesions des Acides Nucleiques," SCIB/DRFMC, CEA/Grenoble, France
Jean-Luc Ravanat
Laboratoire "Lesions des Acides Nucleiques," SCIB/DRFMC, CEA/Grenoble, France
Anthony Romieu
Laboratoire "Lesions des Acides Nucleiques," SCIB/DRFMC, CEA/Grenoble, France
Sylvie Sauvaigo
Laboratoire "Lesions des Acides Nucleiques," SCIB/DRFMC, CEA/Grenoble, France

ABSTRACT

Most of the reactions induced by ·OH radicals (indirect effects) and by one-electron oxidation (direct effects) as the result of exposure to ionizing radiation may be described for the four main DNA nucleobases. Relevant information is now available on the formation of single and tandem base lesions implicating guanine as the most susceptible DNA component to the deleterious effects of ionizing radiation. In contrast, there is still a paucity of information on the radiation-induced formation of base damage within cellular DNA. This is mostly a result of difficulties associated with the measurement of oxidized purine and pyrimidine bases that appear to be generated in very low yields. This is illustrated by the measurement of low amounts of E. coli formamidopyrimidine glycosylase- and endonuclease-III-sensitive sites in the DNA of neoplastic monocytes upon exposure to gamma rays (48 and 53 per 109 bases and per Gy, respectively) using a modified comet assay (the overall number of strand breaks and alkali-labile sites was estimated to be 130 per 109 bases and per Gy). More specifically, the level of several radiation-induced modified bases, including thymine glycols, 5-formyluracil, 5-(hydroxymethyl)uracil, 8-oxo-7,8-dihydroguanine, and 8-oxo-7,8-dihydroadenine, together with related formamidopyrimidine derivatives was assessed using the suitable HPLC-MS/MS method. Information is also provided on the substrate specificity of DNA repair enzymes and the mutagenic potential of base lesions using site-specific modified oligonucleotides as the probes.