| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-01-08 |
| タイトル |
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タイトル |
The impact of DNA double-strand break repair pathways throughout the carbon-ion Spread-out Bragg peak beam |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Dylan Buglewicz
Jessica K.F. Buglewi
Hirakawa Hirokazu
Kato Takamitsu
Cuihua Liu
YaQun Fang
Kusumoto Tamon
Fujimori Akira
Sai Sei
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Following carbon-ion beam irradiation in mammalian cells, such as used in carbon-ion radiotherapy (CIRT), it has been suggested that the balance between whether non-homologous end joining (NHEJ) or homologous recombination (HR) is utilized depends on the DNA double-strand break (DSB) complexity. Here, we quantified DSB distribution and identified the importance of each DNA double-strand break (DSB) repair pathway at increasing depths within carbon-ion Spread-out Bragg peak (SOBP) beam range. CHO cell lines were irradiated in a single-biological system capable of incorporating the full carbon-ion SOBP beam range. Cytotoxicity and DSB distribution/repair kinetics were examined at increasing beam depths using cell survival as an endpoint and γ-H2AX as a surrogate marker for DSBs. We observed that proximal-SOBP had highest number of total foci/cell and lowest survival while distal-SOBP had most dense tracks. Both NHEJ- and HR-deficient CHO cells portrayed an increase in radiosensitivity throughout the full carbon-beam range. Although, NHEJ-deficient cells were most radiosensitive cell line from beam entrance up to proximal-SOBP and demonstrated a dose-dependent decrease in ability to repair DSBs. In contrast, HR-deficient cells had greatest ratio of survival fraction at entrance depth to lowest survival fraction within SOBP and demonstrated an LET-dependent decrease in ability to repair DSBs. Collectively, our results provide insights on treatment planning and potential targets to inhibit as HR was a more beneficial pathway to inhibit over NHEJ to enhance cell killing effect of CIRT in targeted tumor cells within SOBP while maintaining limited unwanted damage to surrounding healthy cells. |
| 書誌情報 |
Cancer Science
巻 114,
号 12,
p. 4548-4557,
発行日 2023-10
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| 出版者 |
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出版者 |
WILEY ONLINE LIBRARY |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1349-7006 |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.1111/cas.15972 |
