High-LET radiation induces large amounts of rapidly-repaired sublethal damage.
High-LET radiation induces large amounts of rapidly-repaired sublethal damage.
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高质量辐射会诱导大量快速修复的上生损害。
DOI：
10.1038/s41598-023-38295-3
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发表时间：
2023-07-11
影响因子：
4.6
通讯作者：
McMahon, Stephen J. J.
中科院分区：
文献类型：
--
作者：
Liberal, Francisco D. C. Guerra;Thompson, Shannon J. J.;Prise, Kevin M. M.;McMahon, Stephen J. J.
人们一致认为，高LET辐射作为单一治疗时具有较高的相对生物学有效性（RBE），但它如何与不同质量的辐射（如X射线）相互作用尚不清楚。我们试图通过对X射线和α粒子组合的响应进行量化和建模来澄清这些影响。将细胞暴露于X射线、α粒子或组合，具有不同的剂量和时间间隔。通过53BP1免疫荧光法评估DNA损伤，并使用克隆形成试验评估放射敏感性。然后应用机械模型来了解修复和生存的趋势。与X射线相比，α粒子暴露中53BP1病灶产率显著降低，但这些病灶修复缓慢。虽然单独的α粒子没有表现出轨道间的相互作用，但在X射线和α粒子之间观察到了大量的相互作用。机械模型表明，亚致死损伤（SLD）修复与辐射质量无关，但α粒子产生的亚致死损伤比类似剂量的X射线多得多。这种高RBE可能导致不同辐射质量组合的意外协同作用，这在治疗设计中必须考虑到，并且这种损伤的快速修复可能会影响对高LET的辐射响应的机械建模。
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, . 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.
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影响因子：
2
作者：
Furusawa Y;Nakano-Aoki M;Matsumoto Y;Hirayama R;Kobayashi A;Konishi T
通讯作者：
Konishi T
影响因子：
3.4
作者：
BIRD, RP;ZAIDER, M;ROHRIG, N
通讯作者：
ROHRIG, N
影响因子：
4.3
作者：
Ingram SP;Henthorn NT;Warmenhoven JW;Kirkby NF;Mackay RI;Kirkby KJ;Merchant MJ
通讯作者：
Merchant MJ
影响因子：
5.7
作者：
Demizu, Y;Kagawa, K;Sugimura, K
通讯作者：
Sugimura, K
影响因子：
2.6
作者：
Leatherbarrow, EL;Harper, JV;O'Neill, P
通讯作者：
O'Neill, P