Mechanisms of Mitochondrial Cell Death Induced by Radiation

点击翻译按钮获取中文摘要

Mitochondrial DNA codes 13 components of electron transport chain. Lacking of mtDNA abrogates the electron transport system. We hypothesize that mitochondria deficient in functional electron transport system can result in increased production of superoxide and thus more oxidative stress. Sensitivity to X-rays, clonogenicity, frequency of double strand breaks(DSB), chromosome aberration, free radical generation, apoptosis and oxidative damage markers were examined in 143B human oseteosarcoma cell line (Rho+) and mtDNA-less (Rho0) cells derived from this cell line. No significant difference was observed between Rho+ and Rho0 cells without X-rays exposure for frequency of DSB and chromosome aberration. Clonogenicity assay showed greater sensitivity in Rho0 cells compared to Rho+ cells exposed to X-rays. More DSBs, and more chromosome aberrations in terms of gap, translocation, and deletion were observed in Rho0 cells. Substitution of normal mitochondria including mitochondrial DNA resulted recover of X-ray sensitivity. These results suggest that Rho0 cells lacking mtDNA has more oxidative stress and higher sensitivity to X-rays. Furthermore, the chromosomal damage by irradiation was restored substantially by Vitamin E.