Protective effects induced following the exposure to modulated radiation intensity reduce importance of dose-rate effects

Matsuya, Yusuke  ; McMahon, S.*; Ghita, M.*; Sato, Tatsuhiko   ; Yoshii, Yuji*; Kai, Takeshi   ; Date, Hiroyuki*; Prise, K.*

Under non-uniform exposure caused in modern radiotherapy (i.e., IMRT, VMAT and Cyberknife), intercellular signalling and DNA repair during irradiation play important roles in the induction of increased cell survival (radio-resistance). However, the underlying mechanisms which induce radio-resistance following such exposures remain unclear. In this study, to investigate the impact of modulated radiation intensity on radio-sensitivity, we performed cell experiments and developed model analysis, and evaluated the cell survival and DNA strand break yield. In this experiment, the dose was delivered to 50% of the area of the flask containing cells. In model development, we also modelled cell responses considering dose-rate effects and signaling effects. As a result, in comparison with uniform-field exposure, the non-uniform irradiation reduces the initial yield of DNA damage in directly irradiated cells, leading to higher cell survival, whilst the importance of cell recovery during irradiation (dose-rate effects) was reduced. This work suggests that the radio-resistance in directly irradiated cells is predominantly attributed to initial protective effects after non-uniform irradiation.