Impact of mitochondrial DNA on radiation sensitivity of transformed human fibroblast cells: clonogenic survival, micronucleus formation and cellular ATP level.
The purpose of this study was to evaluate the impact of mitochondrial DNA (mtDNA) on the radiation sensitivity of transformed human fibroblast cells. The p+ and p0 human fibroblast cell lines were used, which carry wild-type mtDNA and no mtDNA, respectively. Clonogenic radiosensitivity was evaluated by colony formation assay and micronucleus (MN) formation assay. The ATP assay was then used to address the discrepancy between the results of the former two assays. Despite the lack of a significant difference in survival in the colony formation assay, p+ and p0 cells exhibited high and low radiosensitivities, respectively, in the MN formation assay (P < 0.003). This difference in MN formation correlated with high and low levels of cellular ATP content in p+ and p0 cells (P = 0.004). The addition of antimycin A suppressed differences in both MN formation and cellular ATP content. In the transformed human fibroblast cells we used, mtDNA played an important role in radiation-induced MN formation that was correlated with the levels of cellular ATP content. These results may imply the presence of an MN expression pathway that is dependent on the intrinsic ATP level and that may be compensated and lead to an equivalent level of clonogenic survival.
Yoshioka
Yasuo
Y
Department of Multidisciplinary Radiotherapy, Osaka University Graduate School of Medicine, Osaka, Suita, 565-0871, Japan. yoshioka@radonc.med.osaka-u.ac.jp
Yamazaki
Hideya
H
Yoshida
Ken
K
Ozeki
Shuji
S
Inoue
Takehiro
T
Yoneda
Makoto
M
Inoue
Toshihiko
T
D000255:Adenosine Triphosphate / Q000378:metabolism*; D002461:Cell Line, Transformed; D004272:DNA, Mitochondrial / Q000502:physiology*; D005347:Fibroblasts / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D048629:Micronuclei, Chromosome-Defective; D011836:Radiation Tolerance / Q000502:physiology*
D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate