NHEJ repair rather than HR repair is the primary function to target to enhance radiosensitization at high LET values

Takahashi, Akihisa*; Kubo, Makoto*; Igarashi, Chie*; Yoshida, Yukari*; Funayama, Tomoo; Kobayashi, Yasuhiko; Nakano, Takashi*

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 82, 2015/03

https://doi.org/10.11484/jaea-review-2014-050

DNA double-strand breaks (DSBs) induced by ionizing radiation pose a major threat to cell survival. The cell can respond to the presence of DSBs, through two major repair pathways: Homologous recombination (HR) and non-homologous end-joining (NHEJ). Higher levels of cell death are induced by high-LET radiation when compared to low-LET radiation, even at the same doses because of less effective or more inefficient DNA repair. In this study, we examine the effects of radiation with different LET values on DNA DSB repair and radiosensitivity. Wild-type cells and HR deficient (but NHEJ proficient) cells exhibited the high RBE values at LET values of 108 keV/ m. The RBE value for each cell type decreased with increasing LET values over 200 keV/m. Although NHEJ proficient cells had an almost constant SER value, NHEJ deficient cells showed a high SER value when compared to NHEJ proficient cells, even with increasing LET values.