@article{oai:repo.qst.go.jp:00046983, author = {Takahashi, Akihisa and Makoto, Kubo and Hongyu, Ma and Akiko, Nakagawa and Yoshida, Yukari and Isono, Mayu and Kanai, Tatsuaki and Ohno, Tatsuya and Furusawa, Yoshiya and Funayama, Tomoo and Kobayashi, Yasuhiko and Nakano, Takashi and 高橋 昭久 and 吉田 由香里 and 磯野 真由 and 金井 達明 and 大野 達也 and 古澤 佳也 and 舟山 知夫 and 小林 泰彦 and 中野 隆史}, issue = {3}, journal = {Radiation Research}, month = {Sep}, note = {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-linear energy transfer (LET) radiation when compared to low-LET radiation, even at the same physical doses, due to less effective and efficient DNA repair. To clarify whether high-LET radiation inhibits all repair pathways or specifically one repair pathway, studies were designed to examine the effects of radiation with different LET values on DNA DSB repair and radiosensitivity. Embryonic fibroblasts bearing repair gene (NHEJ-related Lig4 and/or HR-related Rad54) knockouts (KO) were used and their responses were compared to wild-type cells. The cells were exposed to X rays, spread-out Bragg peak (SOBP) carbon ion beams as well as with carbon, iron, neon and argon ions. Cell survival was measured with colony-forming assays. The sensitization enhancement ratio (SER) values were calculated using the 10% survival dose of wild-type cells and repair-deficient cells. Cellular radiosensitivity was listed in descending order: double-KO cells . Lig4-KO cells . Rad54-KO cells . wild-type cells. Although Rad54-KO cells had an almost constant SER value, Lig4-KO cells showed a high-SER value when compared to Rad54-KO cells, even with increasing LET values. These results suggest that with carbon-ion therapy, targeting NHEJ repair yields higher radio sensitivity than targeting homologous recombination repair.}, pages = {338--344}, title = {Nonhomologous End-Joining Repair Plays a More Important Role than Homologous Recombination Repair in Defining Radiosensitivity after Exposure to High-LET Radiation}, volume = {182}, year = {2014} }