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Radiosensitization Effect of PARP Inhibition in Cells Exposed to Low and High LET Radiation
https://repo.qst.go.jp/records/46336
https://repo.qst.go.jp/records/4633648038c27-e178-4671-9cf7-ec08eda3783f
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-06-05 | |||||
| タイトル | ||||||
| タイトル | Radiosensitization Effect of PARP Inhibition in Cells Exposed to Low and High LET Radiation | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Hirai, Takahisa
× Hirai, Takahisa× Shirai, Hidenori× Fujimori, Hiroaki× Okayasu, Ryuichi× Sasai, Keisuke× Masutani, Mitsuko× 平井 崇久× 白井 秀徳× 岡安 隆一× 笹井 啓資× 益谷 美都子 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 書誌情報 |
Cancer Science 巻 103, 号 6, p. 1045-1050, 発行日 2012-06 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1347-9032 | |||||
