@article{oai:repo.qst.go.jp:00046336,
 author = {Hirai, Takahisa and Shirai, Hidenori and Fujimori, Hiroaki and Okayasu, Ryuichi and Sasai, Keisuke and Masutani, Mitsuko and 平井 崇久 and 白井 秀徳 and 岡安 隆一 and 笹井 啓資 and 益谷 美都子},
 issue = {6},
 journal = {Cancer Science},
 month = {Jun},
 note = {Poly(ADP-ribose) polymerase (PARP)-1 promotes base excision repair and DNA strand break repair. Inhibitors of PARP enhance the cytotoxic effects of gamma- and X-irradiation. We investigated the impact of PARP inhibition on the responses to gamma-irradiation (low LET (liner energy transfer) radiation) and carbon-ion irradiation (high LET radiation) in the human pancreatic cancer cell line MIA PaCa-2. Cell survival was assessed by colony formation assay after combination treatment with the PARP inhibitor AZD2281 and single fraction gamma-irradiation and carbon-ion irradiation (LET 13 and 70 keV/um). The DNA damage response (DDR) was assessed by pulse field gel electrophoresis (PFGE), Western blotting and flow cytometry. Treatment with a PARP inhibitor enhanced the cytotoxic effect of gamma-, LET 13 and LET 70 carbon-ion irradiation. Moreover, the radiosensitization effect was greater for LET 70 than for LET 13 irradiation. Prolonged and increased levels of gamma-H2AX were observed both after gamma- and carbon-ion irradiation in the presence of the PARP inhibitor. Enhanced level of phosphorylated-p53 (Ser-15) was observed after gamma-irradiation but not after carbon-ion irradiation. PARP inhibitor treatment induced S phase arrest and enhanced subsequent G2/M arrest both after gamma- and carbon-ion irradiation. These results suggest that the induction of S phase arrest through an enhanced DDR and a local delay in DNA double strand break processing by PARP inhibition caused sensitization to gamma- and carbon-ion irradiation. Taken together, PARP inhibitors might be applicable to a wide therapeutic range of LET radiation through their effects on the DDR.},
 pages = {1045--1050},
 title = {Radiosensitization Effect of PARP Inhibition in Cells Exposed to Low and High LET Radiation},
 volume = {103},
 year = {2012}
}