title: The nucleotide pool, a target for low-dose gamma-ray-induced oxidative stress.
abstract: Oxidative stress occurs when the generation of reactive oxygen species (ROS) exceeds the cellular antioxidant capacity. The excess ROS react with and modify cellular components. Nucleic acid modifications are of principal interest because they may cause mutations. 8-Oxo-7,8-dihydro-2 -deoxyguanosine (8-oxo-dG) is a mutagenic lesion that can be formed by ROS in DNA as well as in the nucleotide pool. 8-Oxo-dG is removed from the DNA by base excision repair and from the nucleotide pool by the nucleotide sanitization enzyme hMTH1. hMTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, which is released to the extracellular environment and can serve as a marker of oxidative stress. The aim of this work was to establish the dose-response relationship for radiation-induced extracellular 8-oxo-dG and hMTH1 in the mGy range of gamma rays in three cellular model systems: human whole blood, human fibroblasts and stimulated lymphocytes. Extracellular 8-oxo-dG was analyzed with the use of an ELISA and hMTH1 by Western blotting. Our results demonstrate that low-dose ionizing radiation induces a stress response that leads to the formation of extracellular 8-oxo-dG and induction of hMTH1 in all three cellular model systems tested. This suggests that the nucleotide pool is an important target for radiation-induced stress response.
authors.affiliation: Department of Genetics, Stockholm University, Stockholm, Sweden.
authors.forename: Traimate
authors.initials: T
authors.lastname: Sangsuwan
authors.forename: Siamak
authors.initials: S
authors.lastname: Haghdoost
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002460:Cell Line; D045643:DNA Repair Enzymes / Q000097:blood / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005110:Extracellular Space / Q000378:metabolism / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000528:radiation effects; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D009711:Nucleotides / Q000378:metabolism*; D018384:Oxidative Stress / Q000528:radiation effects*; D010744:Phosphoric Monoester Hydrolases / Q000097:blood / Q000378:metabolism; D011829:Radiation Dosage
chemical_list: D009711:Nucleotides; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010744:Phosphoric Monoester Hydrolases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes; D003849:Deoxyguanosine