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Journal of Environmental Pathology, Toxicology and Oncology

ISSN for PRINT: 0731-8898

Institutional price:	$672.00
Issues per year:	4

Best Paper Award Selection - Editorial Board Site

2004, Volume23

88 pages

DOI: 10.1615/JEnvPathToxOncol.v23.i1

Issue price - $160.00

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.