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BEST IN PHYSICS (THERAPY): The Nonhomologous End-Joining Repair Pathway Determines Cell Radiosensitivity in Helium and Carbon Ion Beam

https://repo.qst.go.jp/records/77370
https://repo.qst.go.jp/records/77370
c128e8eb-8c5f-4897-8824-35b8dc9c366a
Item type 一般雑誌記事 / Article(1)
公開日 2019-11-09
タイトル
タイトル BEST IN PHYSICS (THERAPY): The Nonhomologous End-Joining Repair Pathway Determines Cell Radiosensitivity in Helium and Carbon Ion Beam
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 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 Flint, D.

× Flint, D.

WEKO 1070756

Flint, D.

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Bright, S.

× Bright, S.

WEKO 1070757

Bright, S.

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McFadden, C.

× McFadden, C.

WEKO 1070758

McFadden, C.

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Chakraborty, S.

× Chakraborty, S.

WEKO 1070759

Chakraborty, S.

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Yoon, D.

× Yoon, D.

WEKO 1070760

Yoon, D.

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Shaitelman, S.

× Shaitelman, S.

WEKO 1070761

Shaitelman, S.

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Kodaira, S.

× Kodaira, S.

WEKO 1070762

Kodaira, S.

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Konishi, T.

× Konishi, T.

WEKO 1070763

Konishi, T.

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Sawakuchi, G.

× Sawakuchi, G.

WEKO 1070764

Sawakuchi, G.

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Satoshi, Kodaira

× Satoshi, Kodaira

WEKO 1070765

en Satoshi, Kodaira

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Teruaki, Konishi

× Teruaki, Konishi

WEKO 1070766

en Teruaki, Konishi

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抄録
内容記述タイプ Abstract
内容記述 Purpose: To highlight the importance of nonhomologous end-joining (NHEJ) repair in governing a cell’s radiosensitivity to helium and carbon ion beams of varying linear energy transfer (LET). Methods: We selected a pair of isogenic human cancer cell lines with differing proficiency in nonhomologous end-joining (NHEJ) repair, the M059K (NHEJ-proficient) and M059J (NHEJ-deficient) glioblastoma cell lines, and as additional reference cell lines, we selected the H1299 nonsmall cell lung cancer and H460 large cell lung cancer cell lines. We exposed these cells to unmodulated helium and carbon ion beams with nominal energies of 150 and 290 MeV/u, respectively, using energy degraders to achieve LETs ranging from 2.2 to 60 keV/lm. We performed clonogenic assays to calculate the relative biological effectiveness (RBE) of each cell line in these conditions, relative to their survival in 6 MV x-rays, using the dose for 10% survival as the biological endpoint. To support the survival data, we performed immunohistochemical staining of DNA double strand break (DSB) markers (including cH2AX and 53BP1) 30 min and 24 h post irradiation to identify persistent radiation-induced foci. Results: The RBE of the NHEJ-deficient M059J cell line showed significantly less LET dependence than the reference cell lines (increasing only to 1.37 0.07 at 60 keV/lm for M059J versus 1.80 0.10, 1.79 0.04 and 1.98 0.05 for M059K, H460 and H1299, respectively), despite M059J being more radiosensitive to all LETs. Preliminary analysis of foci data for protonexposed cells indicate that the M059J cells have more persistent DSB repair foci 24 h postirradiation (up to a factor of 2.4 0.5 for cH2AX foci), consistent with their deficiency in DNA DSB repair. Conclusion: Our results indicate that proficiency status in NHEJ is extremely important in determining how cell radiosensitivity varies with He- and C-ion LET.
書誌情報 MEDICAL PHYSICS

巻 46, 号 6, p. E457-E457, 発行日 2019-06
出版者
出版者 John Wiley & Sons, Inc
関連サイト
識別子タイプ DOI
関連識別子 https://doi.org/10.1002/mp.13589
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