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Comparison of the bromodeoxyuridine-mediated sensitization effects between low-LET and high-LET ionizing radiation on DNA double-strand breaks
https://repo.qst.go.jp/records/46553
https://repo.qst.go.jp/records/46553d95dfb59-18fd-4dc4-887d-17b0d49f43aa
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2013-05-24 | |||||
| タイトル | ||||||
| タイトル | Comparison of the bromodeoxyuridine-mediated sensitization effects between low-LET and high-LET ionizing radiation on DNA double-strand breaks | |||||
| 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 |
Fujii, Yoshihiro
× Fujii, Yoshihiro× Genet, Matthew× Roybal, Erica× Kubota, Nobuo× Okayasu, Ryuichi× Kiyoshi, Miyagawa× Fujimori, Akira× Kato, Takamitsu× 藤井 義大× ジェネ マシュー× 窪田 宜夫× 岡安 隆一× 藤森 亮× 加藤 宝光 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The incorporation of halogenated pyrmidines such as bromo- and iodo-deoxyuridines (BrdU, IdU) into DNA as thymidine analogs enhances cellular radiosensitivity when high-linear energy transfer (LET) radiation is not used. Although it is known that high-LET ionizing radiation confers fewer biological effects resulting from halogenated pyrimidine incorporation, the exact mechanisms of reduced radiosensitivity with high-LET radiation are not clear. We investigated the radiosensitization effects of halogenated pyrimidines with high-LET radiation using accelerated carbon and iron ions. Cells synchronized into the G1 phase after unifilar (1 cell cycle) and bifilar (2 cell cycles) substitution with 10 uM BrdU were exposed to various degrees of LET with heavy ions and X-rays. We then carried out a colony formation assay to measure cell survival. The gamma-H2AX focus formation assay provided a measure of DNA double-strand break (DSB) formation and repair kinetics. Chromosomal aberration formations for the first post-irradiation metaphase were also scored. For both low-LET X-rays and carbon ions (13 keV/um), BrdU incorporation led to impaired DNA repair kinetics, a larger initial number of DNA DSBs more frequent chromosomal aberrations at the first post-irradiated metaphase, and increased radiosensitivity for cell lethality. The enhancement ratio was higher after bifilar substitution. In contrast, no such synergistic enhancements were observed after high-LET irradiation with carbon and iron ions (70 and 200 keV/um, respectively), even after bifilar substitution. Our results suggest that BrdU substitution did not modify the number and quality of DNA DSBs produced by high-LET radiation. The incorporation of halogenated pyrimidines may produce more complex/clustered DNA damage along with radicals formed by low-LET ionizing radiation. In contrast, the severity of damage produced by high-LET radiation may undermine the effects of BrdU and account for the observed minimal radiosensitization effects. | |||||
| 書誌情報 |
Oncology Reports 巻 29, 号 6, p. 2133-2139, 発行日 2013-06 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1021-335X | |||||
