Seminarium Fizyki Wielkich Energii

A particular problem of modern external beam radiotherapy like IMRT and proton therapy is associated with simultaneous exposure of patients to the therapeutic beam and scattered neutrons with a high relative biological effectiveness (RBE). The interesting question is whether the high and low LET radiations act in a synergistic or additive manner. If they act additively, then the risk of radiotherapy-induced cancer can be deduced from the results of exposures to the single agents. Otherwise, RBE values must be generated for the mixed exposure scenarios or corrected to account for the synergism.The goal of this study is to analyse the kinetics of formation and repair of ionising radiation-induced DNA repair foci in cells exposed to a particles, X-rays and a mixed beam of both. We focus on studying if exposure to mixed beams leads to the formation of clustered damage which poses serious problems for the DNA repair machinery. Increased damage complexity following exposure to mixed beams will suggest a higher than expected risk of cancer induction by modern radiotherapy.Human U2OS cells were transfected with plasmids coding for the DNA repair proteins 53BP1 that are tagged with the green fluorescence protein. Cells were exposed to mixed beams in a dedicated exposure facility installed at the Stockholm University. The facility is composed of an YXLON 200 X-rays source and a 50 MBq Am-241 alpha source kept inside a 37oC cell incubator. Spatiotemporal dynamics of 53BP1 foci formation and repair was recorded by time-lapse photography and image analysis.