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アイテム
Radiosensitization Effect of PARP Inhibitor in Cells Exposed to Low and High LET Radiation
https://repo.qst.go.jp/records/70666
https://repo.qst.go.jp/records/7066681cf54c5-d609-4d17-9974-4d3aae17d9f6
| アイテムタイプ | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-12-28 | |||||
| タイトル | ||||||
| タイトル | Radiosensitization Effect of PARP Inhibitor 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_c94f | |||||
| 資源タイプ | conference output | |||||
| 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× 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 | Purpose: To improve radiotherapy of cancer patients, development of efficient radiosensitizer is one of the most important issues in clinical cancer treatment. Poly (ADP-ribose) polymerase (PARP)-1 is a nuclear enzyme that promotes base excision repair and DNA strand break repair. Inhibitors of PARP have been shown to enhance the cytotoxic effects of ionizing radiation and DNA damaging agents. We investigated the impact of inhibition of PARP on responses to gamma-irradiation (low LET (liner energy transfer) radiation) and carbon-ion irradiation (high LET radiation) in human pancreatic cancer cell line MIA PaCa-2. Methods and Materials: We measured the cell survival by a colony formation assay under combination of PARP inhibitor AZD2281 (one of PARP inhibitors used in clinical trials) and single fraction of gamma-irradiation and carbon-ion irradiation (LET 13 and 70 keV/um). We also analyzed the effect on DNA damage response (DDR) by pulse field gel electrophoresis (PFGE), western blotting and flow cytometry. Results: The colony formation assay showed that addition of PARP inhibitor enhanced the effect of gamma-, LET 13 and LET 70 carbon-ion irradiation on cell survival compared to irradiation alone. Increased levels of gamma-H2AX and phosphorylated p53 (p-p53) (Ser-15) were observed after gamma-irradiation in the presence of PARP inhibitor. We also observed increased levels of gamma-H2AX both after LET 13 and 70 keV/m carbon-ion irradiation, but the increased level of p-p53 was not detected. These results suggest that PARP inhibitor enhances DDR and a local delay in DNA double strand break (DSB) processing after irradiation, whereas after in carbon-ion irradiation these occurred independenty from p53 phosphorylation status. Attenuated level of phosphorylated histone H3 was observed after gamma- and carbon-ion irradiation in the presence of AZD2281, suggesting an increase of S phase arrest. PARP inhibitor induced S phase arrest and subsequent G2/M arrest both after gamma and carbon-ion irradiation in flow cytometry, suggesting that the S phase arrest might contribute to cell death. Conclusion: PARP inhibitor AZD2281 sensitized both gamma- and carbon-ion irradiated MIA PaCa-2 cells. Enhanced and prolonged DDR by AZD2281 were observed. PARP inhibitor may be useful when combined with low or high LET radiation in cancer therapy. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | The 53rd Annual Meeting of the American Society For Therapeutic Radiology and Radiation Oncology (ASTRO) | |||||
| 発表年月日 | ||||||
| 日付 | 2011-10-06 | |||||
| 日付タイプ | Issued | |||||
