Department of Oncology, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, Göteborg, Sweden.
Int J Radiat Biol. 2011 Apr;87(4):372-84. doi: 10.3109/09553002.2011.538127. Epub 2010 Dec 21.
To investigate cell cycle effects and relative biological effectiveness (RBE) of α-particles from the clinically relevant radionuclide Astatine-211 ((211)At), using X-rays as reference radiation. Double-strand breaks (DSB), non-DSB clusters containing oxidised purines and clonogenic survival were investigated.
Asynchronous V79-379A fibroblasts or cells synchronised with mimosine in G1, early, mid and late S phase or in mitosis were irradiated with X-rays (100 kV(p)) or (211)At (mean linear energy transfer (LET) 110 keV/μm). Induction of DSB and clusters was determined using pulsed-field gel electrophoresis with fragment analysis. Cell survival was obtained with the clonogenic assay.
In asynchronous cells RBE for DSB- and cluster-induction was 3.5 and 0.59, respectively. RBE for 37% cell survival was 8.6. In different cell cycle phases RBE varied from 1.8-3.9 for DSB and 3.1-7.9 for 37% survival (survival at 2 Gy was 6.9-38 times lower after α-irradiation). (211)At induced 6 times more DSB and X-rays induced 11 times more DSB in mitotic cells with highly compacted chromatin relative G1.
The radio-response is cell cycle dependent and differs between proliferating and non-cycling cells for both low- and high-LET radiation, resulting in a variation in RBE of α-particles between 1.8 and 8.6.
用 X 射线作为参考辐射，研究临床相关放射性核素砹-211((211)At)的α粒子的细胞周期效应和相对生物效应（RBE）。研究了双链断裂（DSB）、含有氧化嘌呤的非双链断裂簇和克隆存活。
用 X 射线（100 kV(p)）或（211）At（平均线性能量转移（LET）110 keV/μm）照射异步 V79-379A 成纤维细胞或用丝裂霉素同步化的 G1、早期、中期和晚期 S 期或有丝分裂中的细胞。用脉冲场凝胶电泳和片段分析测定 DSB 和簇的诱导。用克隆形成测定法获得细胞存活。
在异步细胞中，DSB 和簇诱导的 RBE 分别为 3.5 和 0.59。37%细胞存活的 RBE 为 8.6。在不同的细胞周期阶段，DSB 的 RBE 从 1.8-3.9 不等，37%存活的 RBE 从 3.1-7.9 不等（α辐射后，2 Gy 时的存活降低了 6.9-38 倍）。与 G1 时相对疏松的染色质相比，（211）At 诱导的有丝分裂细胞中的 DSB 增加了 6 倍，X 射线诱导的 DSB 增加了 11 倍。
放射反应是细胞周期依赖性的，并且在增殖和非循环细胞中，低 LET 和高 LET 辐射之间的反应不同，导致α粒子的 RBE 在 1.8 到 8.6 之间变化。
