title: Persistence of DNA double-strand breaks in normal human cells induced by radiation-induced bystander effect.
abstract: Our previous study suggested that the DNA double-strand breaks (DSBs) induced by very low X-ray doses are largely due to bystander effects. The aim of this study was to verify whether DSBs created by radiation-induced bystander effects are likely to be repaired. We examined the generation of DSBs in cells by enumeration of phosphorylated ataxia telangiectasia mutated (ATM) foci, which are correlated with DSB repair, in normal human fibroblast cells (MRC-5) after X irradiation at doses ranging from 1 to 1000 mGy. At 24 h after irradiation, 100% (1.2 mGy), 58% (20 mGy), 12% (200 mGy) and 8.5% (1000 mGy) of the initial number of phosphorylated ATM foci were detected. The number of phosphorylated ATM foci in MRC-5 cells treated with lindane, an inhibitor of radiation-induced bystander effects, prior to X irradiation was assessed; phosphorylated ATM foci were not observed at 5 h (20 mGy) or 24 h (200 mGy) postirradiation. We also counted the number of phosphorylated ATM foci in MRC-5 cells cocultured with MRC-5 cells irradiated with 20 mGy. After 48 h of coculture, 81% of the initial numbers of phosphorylated ATM foci remained. These findings suggest that DSBs induced by the radiation-induced bystander effect persist for long periods, whereas DSBs induced by direct radiation effects are repaired relatively quickly.
authors.affiliation: Department of Environmental Health Science, Oita University of Nursing and Health Sciences, 2944-9 Megusuno, Oita 840-1201, Japan. ojima@oita-nhs.ac.jp
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ojima
authors.forename: Asahi
authors.initials: A
authors.lastname: Furutani
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Ban
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kai
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D024201:Bystander Effect / Q000528:radiation effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D018499:Linear Energy Transfer; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014965:X-Rays
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D001556:Hexachlorocyclohexane; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases