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Radiation-quality dependent bystander effects induced in normal human fibroblasts by X-ray, proton and heavy-ion microbeams.

https://repo.qst.go.jp/records/62935
https://repo.qst.go.jp/records/62935
1563662b-c838-4554-8c9a-4516353a8d19
Item type 会議発表用資料 / Presentation(1)
公開日 2008-12-26
タイトル
タイトル Radiation-quality dependent bystander effects induced in normal human fibroblasts by X-ray, proton and heavy-ion microbeams.
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 Suzuki, Masao

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WEKO 621687

Suzuki, Masao

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Furusawa, Yoshiya

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Furusawa, Yoshiya

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Funayama, Tomoo

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Funayama, Tomoo

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Usami, Noriko

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Usami, Noriko

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Fukamoto, Kana

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Fukamoto, Kana

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Yokota, Yuichiro

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Yokota, Yuichiro

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Hamada, Nobuyuki

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Hamada, Nobuyuki

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Konishi, Teruaki

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Konishi, Teruaki

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Tsuruoka, Chizuru

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Tsuruoka, Chizuru

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Yasuda, Nakahiro

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Yasuda, Nakahiro

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Ishikawa, Takahiro

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Ishikawa, Takahiro

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Hua, Liu Cui

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Hua, Liu Cui

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Iso, Hiroyuki

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Iso, Hiroyuki

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Oikawa, Masakazu

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Oikawa, Masakazu

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Imaseki, Hitoshi

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Imaseki, Hitoshi

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Kobayashi, Katsumi

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Kobayashi, Katsumi

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Kobayashi, Yasuhiko

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Kobayashi, Yasuhiko

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鈴木 雅雄

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en 鈴木 雅雄

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古澤 佳也

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宇佐美 徳子

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小西 輝昭

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鶴岡 千鶴

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en 鶴岡 千鶴

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安田 仲宏

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石川 剛弘

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劉 翠華

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磯 浩之

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及川 将一

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今関 等

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小林 克己

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抄録
内容記述タイプ Abstract
内容記述 INTRODUCTION
A central paradigm in radiation biology has been that only cells "hit" by a track of radiation would be affected to induce radiobiological consequences, and cells "not hit" should not be. This paradigm is the basis for the current system for risk estimation from radiation and the risk of radiation-induced cancer after high and moderate doses are relatively well known, based on the data from detailed epidemiological studies of the Japanese atomic bomb survivors in Hiroshima and Nagasaki1). However, it recently has been challenged by so called non-targeted effects, such as bystander effect, and such radiation-induced non-targeted effects may have important implications for risk evaluation of low dose / low dose rate radiations.
There are many reports regarding bystander cellular effects after irradiation with alpha particles derived from 238Pu or helium-ion microbeams. However, only limited sets of studies have examined bystander effects using different ion species lighter or heavier than helium, such as protons and carbon ions. In this study we have been investigating radiation-quality dependence in bystander cellular responses in normal human cells irradiated with different radiation species, such as X rays, protons and heavy ions.
MATERIALS AND METHODS
12C5+-ion microbeams (220 MeV) were produced with the HZ1 port at the TIARA in JAEA3). The irradiation of monochromatic X-ray microbeams (5.35keV) was carried out using the X-ray microbeam irradiation system at the PF (BL-27B) in KEK4). Proton microbeams (3.4MeV) were generated with the SPICE in NIRS. Approximately 6 x 105 exponentially growing cells were inoculated into each of microbeam dish, which was made of acrylic resin ring with 36 mm diameter and attached 7.5 µm-thick polyimide film on the bottom of the ring, 2 days before irradiation. One day before microbeam irradiation, half of the sample dishes were treated with a specific inhibitor of gap-junction mediated cell-cell communication (40 µM ofgannma-isomer of hexachloro-cyclohexane). Irradiation was carried out using a 256 (16 x 16)-cross-stripe method for either C-ion or X-ray microbeam with the beam area of 20µm x 20µm, and a 729 (27 x 27)-cross-stripe method for proton micrbeams with the beam area of 10µm x10µm. In each beam area microbeams were irradiated with 8 delivered C ions, 0.4Gy of monochromatic X rays and 20 delivered protons, respectively. Around 0.2% of the total cells attached on a microbeam dish was hit by each microbeam directly in our cross-stripe-irradiation method. Cell-killing effect was detected as a reproductive cell death using a colony-forming assay. Mutation induction was counted with a 6-thioguanie resistant clone targeted on hprt locus.
RESULTS AND DISCUSSION
The percent cell survival in C-ion-microbeam-irradiated dishes was ranging from 83% to 94%, while from 97% to 100% in microbeam-irradiated dishes with a specific inhibitor of gap-junction mediated cell-cell communication. On the other hand, the percent in cells irradiated with X-ray or proton microbeams was almost 100%, when using with or without a specific inhibitor of gap-junction.
Mutation frequency in cells irradiated with C-ion microbeams was 6 times higher than that in non-irradiated control cells. Although the frequency in cells irradiated with X-ray micobeams was the same level with the control cells, it for proton-microbeam irradiated cells was around 2 times higher that that for the control cells. Furthermore, the mutation induction for both C- and proton-microbeam irradiated cells reduced to the same level with the control cells, when using with a specific inhibitor of gap-junction. In our microbeam-irradiation method, we estimated that the percent of microbeam direct hit cells was around 0.2% of all cells in the dish. We evaluated that the mutation frequency in the C-ion-microbeam irradiated cells detected with our cross-stripe irradiation method was the same level (no detectable mutation induction) with non-irradiated control cells, based on the data using C-ion broad beams (LET=80 keV/µm, 0.4Gy). The result showed that it was detected a higher mutation induction in the C-ion-microbeam irradiated cells than that of the expected frequency of mutation induction. There is clear evidence that C-ion-microbeam irradiated cells have enabled to induce mutation by a bystander cellular response in neighboring cells, which are not directly hit by carbon ions in the same dish, as well as cell-killing effect.
CONCLUSION
Our studies provide clear evidence that radiation-induced bystander effects depend on radiation quality and biological endpoints. Also, gap-junction mediated cell-cell communication play an important role in the bystander effect.
ACKNOWLEDGEMENTS
This study was supported in part by a grant (18310042) from the Japanese Ministry of Education, Culture, Sports, Sciences and Technology.
REFERENCES
1) Pierce D.A. and Preston D.L., Radiat Res 154; 178-186, 2000.
2) Hamada N. et al., Mutat Res 639 ; 35-44, 2008.
3) Funayama T. et al., J Radiat Res 49; 71-82, 2008.
4) Maeda M. et al., J Radiat Res 49; 171-180,2008.
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 8th International Workshop on Microbeam Probes of Cellular Radiation Responses
発表年月日
日付 2008-11-15
日付タイプ Issued
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