Impact of mitochondrial DNA on hypoxic radiation sensitivity in human fibroblast cells and osteosarcoma cell lines.
The purpose of this study was to evaluate the impact of mitochondrial DNA (mtDNA) on radiation sensitivity under hypoxic conditions. The cell lines used were rho+ and rho0, which carry wild-type mtDNA and no mtDNA, respectively. The rho0 cells do not utilize oxygen because they lack the capacity to carry out oxidative phosphorylation. To confirm the role played by mtDNA in different cell lines, two types of cell line were used: human fibroblast and osteosarcoma cells. Radiosensitivity was evaluated by the colony formation assay, micronucleus (MN) formation assay and comet assay. Hypoxia lowered radiosensitivity in all three experiments for all four cell lines. Between rho+ and rho0 cells, no difference was found in the results from the colony formation assay and comet assay. However, higher MN formation was found in rho+ cells than in rho0 cells, not only under room air conditions in both the fibroblast and osteosarcoma cell lines, but also under hypoxic conditions. Therefore, although hypoxia lowers the radiosensitivity in general, the impact of mtDNA persists under hypoxic conditions.
Yamazaki
Hideya
H
Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. hideya10@hotmail.com
Yoshida
Ken
K
Yoshioka
Yasuo
Y
Isohashi
Fumiaki
F
Ozeki
Shuji
S
Koizumi
Masahiko
M
Yoneda
Makoto
M
Inoue
Takehiro
T
D001859:Bone Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D002588:Cesium Radioisotopes; D003114:Colony-Forming Units Assay; D020552:Comet Assay; D004272:DNA, Mitochondrial / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D000860:Hypoxia; D008928:Mitochondria / Q000378:metabolism* / Q000528:radiation effects; D012516:Osteosarcoma / Q000378:metabolism / Q000532:radiotherapy*; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured; D020741:rho GTP-Binding Proteins / Q000502:physiology
D002588:Cesium Radioisotopes; D004272:DNA, Mitochondrial; D020741:rho GTP-Binding Proteins