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J.Health Sci., 51(3), 385-393, 2005
Role of Mitochondrial DNA in Cells Exposed to Irradiation: Generation of Reactive Oxygen Species (ROS) is Required for G2 Checkpoint upon Irradiation
Saori Kawamura,a Daisaku Takai,a Keiko Watanabe,a Jun-ichi Hayashi,b Kazushige Hayakawa,c and Makoto Akashi*, a
aDepartment of Radiation Emergency Medicine, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan, bInstitute of Biological Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan, and cDepartment of Radiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan
Mitochondria have their own genome encoding subunits of the electron transport chain. Using cells lacking mitochondrial DNA (mtDNA, rho0 cells), we studied the role of mtDNA in irradiation. Loss of mtDNA inhibited cell growth and reduced the level of reactive oxygen species (ROS) as compared to rho+ cells. rho+ cells were more resistant to irradiation than rho0 cells. Upon irradiation, rho0 cells showed delayed G2 arrest and decreased ability of a cell to recover from the G2 checkpoint compared to rho+ cells. Irradiation increased the generation of ROS even more in rho+ cells. Irradiation markedly increased the levels of phosphorylated forms of extracellular-regulated kinases, p42 and p44 (ERK1/2) in rho+ cells, whereas phosphorylated levels of the kinases were affected slightly in rho0 cells. Furthermore, inhibition of the ERK pathway led to a delayed G2 arrest and a delayed recovery from the arrest in irradiated rho+ cells, and treatment with NAC also induced dysfunction of the G2 checkpoint in irradiated rho+ cells. These results suggest that the accumulation of ROS potentiated ERK1/2 kinases after irradiation in rho+ cells, leading to less sensitivity to irradiation. Thus, mtDNA is important for the generation of ROS that act as second messenger.
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