Radiation-induced DNA damage: formation, measurement, and biochemical features.
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 10(9) 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 10(9) 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.
Laboratoire "Lésions des Acides Nucléiques," SCIB/DRFMC, CEA/Grenoble, France. jcadet@cea.fr
Jean
J
Cadet
Sophie
S
Bellon
Thierry
T
Douki
Sandrine
S
Frelon
Didier
D
Gasparutto
Evelyne
E
Muller
Jean-Pierre
JP
Pouget
Jean-Luc
JL
Ravanat
Anthony
A
Romieu
Sylvie
S
Sauvaigo
D000818:Animals; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D005720:Gamma Rays; D006801:Humans; D016297:Mutagenesis, Site-Directed; D013379:Substrate Specificity
D004247:DNA; D045643:DNA Repair Enzymes