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Analysis of lethal DNA damage induced by high LET radiation

https://repo.qst.go.jp/records/70533
https://repo.qst.go.jp/records/70533
0fdc2ad6-b70f-49fa-a7e2-64e2fc0fb48e
Item type 会議発表用資料 / Presentation(1)
公開日 2011-09-16
タイトル
タイトル Analysis of lethal DNA damage induced by 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 object
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 Nakano, Toshiaki

× Nakano, Toshiaki

WEKO 692696

Nakano, Toshiaki

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Terato, Hiroaki

× Terato, Hiroaki

WEKO 692697

Terato, Hiroaki

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Hirayama, Ryoichi

× Hirayama, Ryoichi

WEKO 692698

Hirayama, Ryoichi

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Uzawa, Akiko

× Uzawa, Akiko

WEKO 692699

Uzawa, Akiko

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Furusawa, Yoshiya

× Furusawa, Yoshiya

WEKO 692700

Furusawa, Yoshiya

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Ide, Hiroshi

× Ide, Hiroshi

WEKO 692701

Ide, Hiroshi

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中野 敏彰

× 中野 敏彰

WEKO 692702

en 中野 敏彰

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平山 亮一

× 平山 亮一

WEKO 692703

en 平山 亮一

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鵜澤 玲子

× 鵜澤 玲子

WEKO 692704

en 鵜澤 玲子

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古澤 佳也

× 古澤 佳也

WEKO 692705

en 古澤 佳也

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抄録
内容記述タイプ Abstract
内容記述 Ionizing radiation induces a variety of DNA lesions such as base damage, single-strand breaks (SSBs), double-strand breaks (DSBs), and DNA-protein crosslinks (DPCs). DSBs represent part of the clustered DNA damage and are the most potent lethal lesions. They are produced by either as a consequence of the formation of two closely opposed SSBs (prompt DSBs, PDSBs) or the abortive repair of closely opposed base lesions (COBLs). Although the lethal effect of DPCs has not been rigorously examined, it is very likely that extremely bulky DPCs block the progression of DNA and RNA polymerases, exerting a potent lethal effect on cells. In mammalian cells, the relative biological effectiveness (RBE) as measured by cell killing rises with increasing LET values up to 100–200 keV/um. Considering that high LET radiation generates a dense ionization track, it may produce detrimental PDSBs, COBLs, and DPCs efficiently, thereby leading to severe biological consequences. In the present study, we have analyzed the formation of PDSBs, COBLs, and DPCs induced by high LET radiation in vitro and in vivo.
We irradiated supercoiled plasmid and linear lambda DNA with gamma-rays (0.2 keV/um), carbon ion beams (13 keV/um), and iron ion beams (200 keV/um), and quantified PDSBs and COBLs. The yield of PDSBs+COBLs decreased in the order of gamma > carbon > iron, and hence showed an inverse correlation with LET values. Moreover, consistent with this observation, the yield of chromosomal PDSBs of Chinese hamster ovary cells decreased with increasing LET when cells were irradiated with carbon ions beams of different LET values, suggesting that the decrease in the yield of clustered damage with increasing LET is not peculiar to the in vitro irradiation of DNA.
We also irradiated transplanted SCCVII tumors in mouse legs by carbon ion beams and analyzed the formation of PDSBs and DPCs. Although PDSBs and DPCs were formed both in normoxic and hypoxic tumor cells, the yields of PDSBs and DPCs were significantly different under two conditions. The formation of PDSBs was favored in normoxic tumors, whereas that of DPCs was favored in hypoxic tumors, showing an opposite oxygen effect on the formation of PDSBs and DPCs in irradiated tumors.
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 14th International Congress of Radiation Research (ICRR2011)
発表年月日
日付 2011-09-01
日付タイプ Issued
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