Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, UK.
Sci Rep. 2023 Jul 11;13(1):11198. doi: 10.1038/s41598-023-38295-3.
There is agreement that high-LET radiation has a high Relative Biological Effectiveness (RBE) when delivered as a single treatment, but how it interacts with radiations of different qualities, such as X-rays, is less clear. We sought to clarify these effects by quantifying and modelling responses to X-ray and alpha particle combinations. Cells were exposed to X-rays, alpha particles, or combinations, with different doses and temporal separations. DNA damage was assessed by 53BP1 immunofluorescence, and radiosensitivity assessed using the clonogenic assay. Mechanistic models were then applied to understand trends in repair and survival. 53BP1 foci yields were significantly reduced in alpha particle exposures compared to X-rays, but these foci were slow to repair. Although alpha particles alone showed no inter-track interactions, substantial interactions were seen between X-rays and alpha particles. Mechanistic modelling suggested that sublethal damage (SLD) repair was independent of radiation quality, but that alpha particles generated substantially more sublethal damage than a similar dose of X-rays, [Formula: see text]. This high RBE may lead to unexpected synergies for combinations of different radiation qualities which must be taken into account in treatment design, and the rapid repair of this damage may impact on mechanistic modelling of radiation responses to high LETs.
人们普遍认为，高传能线密度（LET）辐射在单次治疗时具有较高的相对生物效应（RBE），但它与不同质量的辐射（如 X 射线）如何相互作用尚不清楚。我们试图通过量化和建模来阐明这些效应X 射线和α粒子组合的反应。细胞分别用 X 射线、α粒子或它们的组合进行照射，剂量和时间间隔不同。通过 53BP1 免疫荧光法评估 DNA 损伤，通过集落形成实验评估放射敏感性。然后应用机制模型来了解修复和存活的趋势。与 X 射线相比，α粒子照射的 53BP1 焦点产量明显减少，但这些焦点修复缓慢。尽管α粒子单独照射没有轨迹间相互作用，但在 X 射线和α粒子之间观察到了显著的相互作用。机制模型表明，亚致死损伤（SLD）修复与辐射质量无关，但与相同剂量的 X 射线相比，α粒子产生的亚致死损伤要多得多，[公式：见文本]。这种高 RBE 可能会导致不同辐射质量的组合产生意想不到的协同作用，在治疗设计中必须考虑到这一点，而且这种损伤的快速修复可能会影响对高 LET 辐射的放射反应的机制模型。
