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Matsuya, Yusuke; McMahon, S. J.*; Ghita, M.*; Yoshii, Yuji*; Sato, Tatsuhiko; Date, Hiroyuki*; Prise, K. M.*
Scientific Reports (Internet), 9(1), p.9483_1 - 9483_12, 2019/07
Times Cited Count：13 Percentile：65.07(Multidisciplinary Sciences)In radiotherapy, intensity modulated radiation fields and complex dose-delivery are used to prescribe doses to tumors. Here, we analyzed the impact of modulated field on radio-sensitivity and cell recovery during irradiation time. The dose was delivered to either 50% of the area of the flask containing cells (half-field) or 100% of the flask (uniform-field). We also modelled cell-killing considering dose-rate effects and intercellular signals. It is found that (i) in-field cell survival under half-field exposure is higher than uniform-field exposure even with the same dose; (ii) the importance of sub-lethal damage repair in normal human skin fibroblast cells under the half-field is reduced; (iii) the increase of cell survival under half-field is predominantly attributed to not rescue effects (increased repair) but protective effects (reduced initial DNA lesion yield). These findings provide new understanding of radio-sensitivity for hit and non-hit cells under non-uniform exposure.
Matsuya, Yusuke; McMahon, S.*; Ghita, M.*; Sato, Tatsuhiko; Yoshii, Yuji*; Kai, Takeshi; Date, Hiroyuki*; Prise, K.*
no journal, ,
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.
