Estimating the impact of indirect action in neutron-induced DNA damage clusters and neutron RBE
Image credit: James ManaladAbstract
Background Neutron radiation protection factors indicate that the risk of neutron-induced stochastic biological effects is higher compared to other types of ionizing radiation and has a strong energy dependence. Recent Monte Carlo studies by Baiocco et al. (2016) and Montgomery et al. (2021) (from our group) simulated neutron radiation on a nuclear DNA model and demonstrated that the energy-dependent radiobiological risk of neutrons can be correlated with the induction of DNA damage clusters, particularly those that contain difficult-to-repair double-strand breaks (DSBs). The main limitation of these studies is that only direct radiation action was investigated. Thus, for a more comprehensive understanding of pre-repair neutron-induced DNA damage, indirect action must be modeled and its impact must be quantified. Methods An open-source algorithm for indirect action available in the TOPAS-nBio track structure Monte Carlo toolkit was adapted into our group’s existing TOPAS and TOPAS-nBio simulation pipeline for neutron and photon radiation. We performed 100 independent simulated irradiations of monoenergetic neutrons from 1 eV to 10 MeV on our existing custom-built nuclear DNA model and scored various types of DNA damage due to direct and indirect action. The yields of DNA damage were stratified according to the damage-inducing action. For the resulting clusters of DNA damage, we determined the average cluster length and lesion count per cluster. This procedure was also performed for 250 keV X-ray photons that served as our reference radiation. We estimated neutron relative biological effectiveness (RBE) by dividing the neutron-inflicted yield of DNA damage clusters by photon-inflicted counterparts. Finally, we compared our RBE results with established radiation protection factors and the previous studies that only modeled direct action. Results Including indirect action significantly increased the yield of DNA damage (the increase varies with damage type). We found that the majority of neutron-induced DNA damage events were isolated simple lesions due to indirect action, while most clustered lesions were hybrid in nature, i.e., contain lesions due to direct and indirect action. As for cluster properties, including indirect action increased the average length of clusters by about 50% and the number of lesions per cluster by about 25%. Our estimated energy-dependent neutron RBE for inducing DNA damage clusters follows similar trends as the established radiation protection factors and the previous direct-action-only estimates, but is lower in magnitude. We found that his lower magnitude is due to the greater impact of indirect action in the yield of photon-induced clustered DNA damage compared to neutron-induced clustered lesions. Conclusion Indirect action has significant effects on radiation-induced DNA damage clusters in terms of yield, length, and lesion count per cluster, and serves to amplify the effects of direct action. The energy-dependent risk of neutron-induced stochastic effects is likely related to, but not completely explained by, the induction of DNA damage clusters. For a more complete model of neutron RBE, the investigation of factors such as DNA damage repair and non-targeted radiation effects is recommended.
James Manalad
PhD Student, Former MSc Student
Logan Montgomery
PhD Student
