Biomedical Physics Division, Faculty of Physics, University of Warsaw, Warsaw, Poland.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
PLoS One. 2023 Jun 12;18(6):e0286902. doi: 10.1371/journal.pone.0286902. eCollection 2023.
DNA double strand breaks (DSBs) are a deleterious form of DNA damage. Densely ionising alpha radiation predominantly induces complex DSBs and sparsely ionising gamma radiation-simple DSBs. We have shown that alphas and gammas, when applied simultaneously, interact in producing a higher DNA damage response (DDR) than predicted by additivity. The mechanisms of the interaction remain obscure. The present study aimed at testing whether the sequence of exposure to alphas and gammas has an impact on the DDR, visualised by live NBS1-GFP (green fluorescent protein) focus dynamics in U2OS cells. Focus formation, decay, intensity and mobility were analysed up to 5 h post exposure. Focus frequencies directly after sequential alpha → gamma and gamma → alpha exposure were similar to gamma alone, but gamma → alpha foci quickly declined below the expected values. Focus intensities and areas following alpha alone and alpha → gamma were larger than after gamma alone and gamma → alpha. Focus movement was most strongly attenuated by alpha → gamma. Overall, sequential alpha → gamma exposure induced the strongest change in characteristics and dynamics of NBS1-GFP foci. Possible explanation is that activation of the DDR is stronger when alpha-induced DNA damage precedes gamma-induced DNA damage.
DNA 双链断裂（DSBs）是一种有害的 DNA 损伤形式。密集电离的α辐射主要诱导复杂的 DSBs，而稀疏电离的γ辐射则诱导简单的 DSBs。我们已经表明，当α射线和γ射线同时应用时，它们的相互作用会产生比预期的相加作用更高的 DNA 损伤反应（DDR）。相互作用的机制仍不清楚。本研究旨在测试在 U2OS 细胞中通过活 NBS1-GFP（绿色荧光蛋白）焦点动力学来观察到的，α射线和γ射线暴露顺序是否会对 DDR 产生影响。在暴露后长达 5 小时内分析焦点形成、衰减、强度和迁移率。顺序α→γ和γ→α暴露后的焦点频率与单独γ射线暴露后的焦点频率相似，但γ→α焦点迅速下降到低于预期的值。单独的α射线和α→γ射线后的焦点强度和面积大于单独γ射线和γ→α射线后的焦点强度和面积。焦点运动通过α→γ被强烈抑制。总的来说，顺序α→γ暴露会引起 NBS1-GFP 焦点特征和动力学的最强变化。可能的解释是，当α射线诱导的 DNA 损伤先于γ射线诱导的 DNA 损伤时，DDR 的激活更强。
