Heemskerk Tim, Groenendijk Celebrity, Rovituso Marta, van der Wal Ernst, van Burik Wouter, Chatzipapas Konstantinos, Lathouwers Danny, Kanaar Roland, Brown Jeremy M C, Essers Jeroen
Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Radiation Science and Technology, Delft University of Technology, Delft, the Netherlands.
Clin Transl Radiat Oncol. 2025 Jan 3;51:100908. doi: 10.1016/j.ctro.2024.100908. eCollection 2025 Mar.
Understanding the cellular and molecular effect of proton radiation, particularly the increased DNA damage complexity at the distal end of the Bragg curve, is current topic of investigation. This work aims to study clonogenic survival and DNA damage foci kinetics of a head and neck squamous cell carcinoma cell line at various positions along a double passively scattered Bragg curve. Complementary studies are conducted to gain insights into the link between cell survival variations, experimentally yielded foci and the number and complexity of double strand breaks (DSBs).
Proton irradiations are performed at the HollandPTC R&D proton beamline, using a double passively scattered setup. A custom water phantom setup is employed to accurately position the samples within the Bragg curve. FaDu cells are irradiated at the proximal 36 % point of the Bragg peak, (P36), proximal 80 % point of the Bragg peak (P80) and distal 20 % point of the Bragg peak (D20), with dose-averaged mean lineal energies ( ) of 1.10 keV/μm, 1.80 keV/μm and 7.25 keV/μm, respectively.
Clonogenic survival correlates strongly with , showing similar survival for P36 (D=3.0 Gy) and P80 (D=2.9 Gy), but decreased survival for D20 (D = 1.6 Gy). D20 irradiated samples exhibit increased 53BP1 foci shortly after irradiation, slower resolution of the foci, and larger residual 53BP1 foci after 24 h, indicating unrepaired complex breaks. These experimental observations are supported by the study which demonstrates that irradiation at D20 leads to a 1.7-fold increase in complex DSBs with respect to the total number of strand breaks compared to P36 and P80.
This combined approach provides valuable insights into the cellular and molecular effect of proton radiation, emphasizing the increased DNA damage complexity at the distal end of the Bragg curve, and has the potential to enhance the efficacy of proton therapy.
了解质子辐射的细胞和分子效应，尤其是布拉格曲线远端DNA损伤复杂性的增加，是当前的研究课题。本研究旨在探讨头颈部鳞状细胞癌细胞系在双被动散射布拉格曲线上不同位置的克隆形成存活率和DNA损伤灶动力学。进行了补充研究，以深入了解细胞存活变化、实验产生的病灶与双链断裂（DSB）的数量和复杂性之间的联系。
在荷兰PTC研发质子束线上使用双被动散射装置进行质子辐照。采用定制的水体模装置将样品精确放置在布拉格曲线内。对FaDu细胞在布拉格峰近端36%点（P36）、布拉格峰近端80%点（P80）和布拉格峰远端20%点（D20）进行辐照，剂量平均平均线能量（ ）分别为1.10 keV/μm、1.80 keV/μm和7.25 keV/μm。
克隆形成存活率与 密切相关，P36（D = 3.0 Gy）和P80（D = 2.9 Gy）的存活率相似，但D20（D = 1.6 Gy）的存活率降低。D20辐照的样品在辐照后不久53BP1病灶增加，病灶分辨率较慢，24小时后残留的53BP1病灶更大，表明存在未修复的复杂断裂。这些实验观察结果得到了 研究的支持，该研究表明，与P36和P80相比，D20处的辐照导致复杂DSB相对于链断裂总数增加1.7倍。
这种综合方法为质子辐射的细胞和分子效应提供了有价值的见解，强调了布拉格曲线远端DNA损伤复杂性的增加，并有可能提高质子治疗的疗效。
