Relating Linear Energy Transfer to the Formation and Resolution of DNA Repair Foci After Irradiation with Equal Doses of X-ray Photons, Plateau, or Bragg-Peak Protons

International Journal of Molecular Sciences

Verena Jendrossek¹  Beate Timmermann²  Sebastian Oeck³  Klaudia Szymonowicz³  Gesa Wiel³  Adam Krysztofiak³  George Iliakis⁴  Benjamin Koska⁵  Jamil Lambert⁵ 

[1] Medical School;University of Duisburg-Essen;Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Virchowstrasse 173, 45122 Essen, Germany;Institute of Medical Radiation Biology;West German Proton Therapy Centre Essen, University Hospital Essen, Am Muehlenbach 1, 45147 Essen, Germany;

关键词: Bragg-peak protons;    plateau protons;    photons;    irradiation;    DNA damage;    foci formation;    linear energy transfer;   

DOI  :  10.3390/ijms19123779

来源: DOAJ

【 摘 要 】

Proton beam therapy is increasingly applied for the treatment of human cancer, as it promises to reduce normal tissue damage. However, little is known about the relationship between linear energy transfer (LET), the type of DNA damage, and cellular repair mechanisms, particularly for cells irradiated with protons. We irradiated cultured cells delivering equal doses of X-ray photons, Bragg-peak protons, or plateau protons and used this set-up to quantitate initial DNA damage (mainly DNA double strand breaks (DSBs)), and to analyze kinetics of repair by detecting γH2A.X or 53BP1 using immunofluorescence. The results obtained validate the reliability of our set-up in delivering equal radiation doses under all conditions employed. Although the initial numbers of γH2A.X and 53BP1 foci scored were similar under the different irradiation conditions, it was notable that the maximum foci level was reached at 60 min after irradiation with Bragg-peak protons, as compared to 30 min for plateau protons and photons. Interestingly, Bragg-peak protons induced larger and irregularly shaped γH2A.X and 53BP1 foci. Additionally, the resolution of these foci was delayed. These results suggest that Bragg-peak protons induce DNA damage of increased complexity which is difficult to process by the cellular repair apparatus.

【 授权许可】

Unknown