RBE of α-particles from 211At for complex DNA damage and cell survival in relation to cell cycle position

Abstract

Purpose: To investigate cell cycle effects and relative biological effectiveness (RBE) of α-particles from the clinically relevant radionuclide Astatine-211 (211At), using X-rays as reference radiation. Double-strand breaks (DSB), non-DSB clusters containing oxidised purines and clonogenic survival were investigated.Materials and methods: 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 kVp) or 211At (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.Results: 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). 211At induced 6 times more DSB and X-rays induced 11 times more DSB in mitotic cells with highly compacted chromatin relative G1.Conclusions: 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.