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 kV_p) 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.

Keywords:

• cell cycle
• clonogenic cell survival
• double-strand breaks
• alpha emitters
• relative biological effectiveness
• clustered damage

Acknowledgements

The authors thank Ulla Delle for flow cytometric analysis, Nicolas Chouin for help with microdosimetric calculations, Jakob Heydorn-Lagerlöf for statistical analysis and Bo Stenerlöw for valuable comments on the manuscript.

Funding: This work was supported by King Gustaf V Jubilee Clinic Research Foundation [2009:36], Assar Gabrielsson Foundation and the Swedish Radiation Safety Authority [1658].

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.