Related Experiment Video
Updated: Sep 1, 2025

Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation
Published on: July 3, 2015
Differential responses to 223Ra and Alpha-particles exposure in prostate cancer driven by mitotic catastrophe
Francisco D C Guerra Liberal1, Hugo Moreira1, Kelly M Redmond1
1The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom.
Introduction:
Radium-223 (223Ra) has been shown to have an overall survival benefit in metastatic castration-resistant prostate cancer (mCRPC) involving bone. Despite its increased clinical usage, relatively little is known regarding the mechanism of action of 223Ra at the cellular level.
Methods:
We evaluated the effects of 223Ra irradiation in a panel of cell lines and then compared them with standard X-ray and external alpha-particle irradiation, with a particular focus on cell survival and DNA damage repair kinetics.
Results:
223Ra exposures had very high, cell-type-dependent RBE50% ranging from 7 to 15. This was significantly greater than external alpha irradiations (RBE50% from 1.4 to 2.1). These differences were shown to be partially related to the volume of 223Ra solution added, independent of the alpha-particle dose rate, suggesting a radiation-independent mechanism of effect. Both external alpha particles and 223Ra exposure were associated with delayed DNA repair, with similar kinetics. Additionally, the greater treatment efficacy of 223Ra was associated with increased levels of residual DNA damage and cell death by mitotic catastrophe.
Conclusions:
These results suggest that 223Ra exposure may be associated with greater biological effects than would be expected by direct comparison with a similar dose of external alpha particles, highlighting important challenges for future therapeutic optimization.
Related Concept Videos
Biological Effects of Radiation
DNA Damage can Stall the Cell Cycle
Other Unique Bacteria
Nucleotide Excision Repair

