title: Mitochondrial dysfunction, a probable cause of persistent oxidative stress after exposure to ionizing radiation.
abstract: Several recent studies have suggested that the reactive oxygen species (ROS) generated from mitochondria contribute to genomic instability after exposure of the cells to ionizing radiation, but the mechanism of this process is not yet fully understood. We examined the hypothesis that irradiation induces mitochondrial dysfunction to cause persistent oxidative stress, which contributes to genomic instability. After the exposure of cells to 5 Gy gamma-ray irradiation, we found that the irradiation induced the following changes in a clear pattern of time courses. First, a robust increase of intracellular ROS levels occurred within minutes, but the intracellular ROS disappeared within 30 min. Then the mitochondrial dysfunction was detected at 12 h after irradiation, as indicated by the decreased activity of NADH dehydrogenase (Complex I), the most important enzyme in regulating the release of ROS from the mitochondrial electron transport chain (ETC). Finally, a significant increase of ROS levels in the mitochondria and the oxidation of mitochondrial DNA were observed in cells at 24 h or later after irradiation. Although further experiments are required, results in this study support the hypothesis that mitochondrial dysfunction causes persistent oxidative stress that may contribute to promote radiation-induced genomic instability.
authors: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Takako
authors: T
authors: Yoshida
authors: Shinji
authors: S
authors: Goto
authors: Miho
authors: M
authors: Kawakatsu
authors: Yoshishige
authors: Y
authors: Urata
authors: Tao-Sheng
authors: TS
authors: Li
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects; D048430:Cell Shape / Q000528:radiation effects; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005720:Gamma Rays; D042822:Genomic Instability; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D009245:NADH Dehydrogenase / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000528:radiation effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D009245:NADH Dehydrogenase; D003849:Deoxyguanosine