O43. Estimating the effectiveness of high LET radiations to induce damage to DNA in human lymphocytes and modelling the repair thereof

Abstract

Introduction Neutron and ion beam irradiations have an increased efficiency in cell killing, resulting from their high linear-energy-transfer (LET) which in turn induces clustered and complex DNA breaks. Similarly, Auger electron irradiations have been shown to a have an increased relative biological effectiveness (RBE) when compared to low-LET radiations. We report on our investigations into the RBE of the DNA incorporated Auger electron emitting 123 I and a model which may estimate the induction and repair of γ -H2AX foci (markers of DNA double strand breaks (DSBs)) in human lymphocytes after exposure to fast neutrons. Materials and methods The RBE of 123 I was determined by comparison of micronuclei inductions in T-lymphocytes using 5-[ 123 I]-iodo-2-deoxyuridine and similar inductions by graded doses of 60 Co γ -rays. Additionally, a theoretical model which describes the time-based repair pathways of DNA DSBs using a set of dependent partial differential equations, was investigated. The validity of the model was assessed by comparing the γ -H2AX foci kinetics predicted by the model to experimental curves observed for lymphocytes exposed to neutrons (20 keV/ μ m) and 60 Co γ -rays. Results The dose-limiting RBE of the DNA incorporated 123 I was found to range from 3 to 11. These observed RBE values relate well to those obtained in studies with 125 I incorporated into rodent cell lines. The higher micronuclei frequencies noted for Auger electrons in the study is indicative of the high-LET nature of these particles. Similar to experimental observations, the theoretical repair model predicted that a larger number of DSBs remain unrepaired after neutron irradiation compared to low-LET γ -irradiation. The model was shown to accurately describe and estimate the kinetics of γ -H2AX foci in human lymphocytes after exposure to fast neutrons and 60 Co γ -rays. Conclusion With respect to their role in radiation therapy and protection, there is a need for investigating and developing models which may predict the induction and repair of high-LET radiation induced DNA damage. Acknowledgement This work was supported by a University Development Cooperation VLIR Own Initiative Programme between Belgium and South Africa.