- 作者：Nicole Grosse ; Andrea O. Fontana ; Eugen B. Hug ; Antony Lomax ; Adolf Coray ; Marc Augsburger ; Harald Paganetti ; Aless ; ro A. Sartori ; Martin Pruschy
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：1 January, 2014
- 年：2014
- 卷：88
- 期：1
- 页码：175-181
- 全文大小：785 K
Purpose
To investigate the impact of the 2 major DNA repair machineries on cellular survival in response to irradiation with the 2 types of ionizing radiation.Methods and Materials
The DNA repair and cell survival endpoints in wild-type, homologous recombination (HR)-deficient, and nonhomologous end-joining-deficient cells were analyzed after irradiation with clinically relevant, low-linear energy transfer (LET) protons and 200-keV photons.
Results
All cell lines were more sensitive to proton irradiation compared with photon irradiation, despite no differences in the induction of DNA breaks. Interestingly, HR-deficient cells and wild-type cells with small interfering RNA-down-regulated Rad51 were markedly hypersensitive to proton irradiation, resulting in an increased relative biological effectiveness in comparison with the relative biological effectiveness determined in wild-type cells. In contrast, lack of nonhomologous end-joining did not result in hypersensitivity toward proton irradiation. Repair kinetics of DNA damage in wild-type cells were equal after both types of irradiation, although proton irradiation resulted in more lethal chromosomal aberrations. Finally, repair kinetics in HR-deficient cells were significantly delayed after proton irradiation, with elevated amounts of residual 纬H2AX foci after irradiation.
Conclusion
Our data indicate a differential quality of DNA damage by proton versus photon irradiation, with a specific requirement for homologous recombination for DNA repair and enhanced cell survival. This has potential relevance for clinical stratification of patients carrying mutations in the DNA damage response pathways.