Department of Nuclear Medicine, University Hospital Würzburg, 97080 Würzburg, Germany.
Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, 80937 Munich, Germany.
Int J Mol Sci. 2024 Aug 7;25(16):8629. doi: 10.3390/ijms25168629.
The combination of high and low LET radionuclides has been tested in several patient studies to improve treatment response. Radionuclide mixtures can also be released in nuclear power plant accidents or nuclear bomb deployment. This study investigated the DNA damage response and DNA double-strand break (DSB) repair in peripheral blood mononuclear cells (PBMCs) after internal exposure of blood samples of 10 healthy volunteers to either no radiation (baseline) or different radionuclide mixtures of the α- and β-emitters [Ra]RaCl and [Lu]LuCl, i.e., 25 mGy/75 mGy, 50 mGy/50 mGy and 75 mGy/25 mGy, respectively. DSB foci and γ-H2AX α-track enumeration directly after 1 h of exposure or after 4 h or 24 h of repair revealed that radiation-induced foci (RIF) and α-track induction in 100 cells was similar for mixed α/β and pure internal α- or β-irradiation, as were the repair rates for all radiation qualities. In contrast, the fraction of unrepaired RIF (Q) in PBMCs after mixed α/β-irradiation (50% Ra & 50% Lu: Q = 0.23 ± 0.10) was significantly elevated relative to pure β-irradiation (50 mGy: Q = 0.06 ± 0.02), with a similar trend being noted for all mixtures. This α-dose-dependent increase in persistent foci likely relates to the formation of complex DNA damage that remains difficult to repair.
高 LET 和低 LET 放射性核素的组合已在多项患者研究中进行了测试，以提高治疗反应。放射性核素混合物也可能在核电站事故或核炸弹部署中释放。本研究调查了 10 名健康志愿者的血液样本在内部暴露于不同的α和β发射体[Ra]RaCl 和[Lu]LuCl 的放射性核素混合物后（25 mGy/75 mGy、50 mGy/50 mGy 和 75 mGy/25 mGy），外周血单个核细胞（PBMCs）中的 DNA 损伤反应和 DNA 双链断裂（DSB）修复。直接在暴露 1 小时后或修复 4 小时或 24 小时后检测 DSB 焦点和γ-H2AX α 轨迹计数，发现混合α/β和纯内部α或β辐照的辐射诱导焦点（RIF）和 100 个细胞中的α轨迹诱导相似，所有辐射质量的修复率也相似。相比之下，混合α/β辐照后（50%Ra 和 50%Lu：Q=0.23±0.10）PBMCs 中未修复的 RIF（Q）分数显著高于纯β辐照（50 mGy：Q=0.06±0.02），所有混合物都存在类似的趋势。这种与α剂量相关的持续焦点增加可能与难以修复的复杂 DNA 损伤的形成有关。
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