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論文

LET dependency of human normal dermal cells survival in carbon ion irradiation

吉田 由香里*; 溝端 健亮*; 松村 彰彦*; 磯野 真由*; 八高 知子*; 中野 隆史*; 舟山 知夫; 小林 泰彦; 金井 達明*

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 81, 2015/03

日本の炭素線治療において臨床線量を決定するために用いられているclinical RBE (cRBE)はexperimental RBE (eRBE)にscaling factorをかけたものである。eRBEはhuman salivary gland(HSG)細胞を用いたコロニー形成法によりlinear-quadratic(LQ)モデルで得られた$$alpha$$値および$$beta$$値から求められた各LETにおけるRBEが採用されており、これが全ての患者(すなわちすべての細胞および組織)における炭素線治療計画に反映されている。しかしながら、RBEは線量,線量率,細胞や組織の種類、エンドポイント、酸素化の程度などにより異なる。そこで、群馬大学重粒子線照射施設(GHMC)のLET 13$$sim$$80keV/$$mu$$m、および原子力機構TIARAのLET 108$$sim$$158keV/$$mu$$mの炭素線を用い、その線量分布を評価すると共に、ヒト正常皮膚細胞への照射を行い、得られたRBE値について過去のHSG細胞の結果と比較・解析した。

論文

NHEJ repair rather than HR repair is the primary function to target to enhance radiosensitization at high LET values

高橋 昭久*; 久保 誠*; 五十嵐 千恵*; 吉田 由香里*; 舟山 知夫; 小林 泰彦; 中野 隆史*

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 82, 2015/03

放射線によるDNA二本鎖切断(DSB)は致命的であるが、相同組換え(HR)および非相同末端結合(NHEJ)によって修復される。そこで、我々は殺細胞効果におよぼすDNA二本鎖切断修復のLET依存性を明らかにすることを目的に、DNA二本鎖切断修復の異なる細胞における高LET放射線感受性をコロニー形成法で評価した。その結果、NHEJがはたらく野生型細胞とHR欠損細胞は108keV/$$mu$$mの炭素線で高いRBE値を示した。SER値はHR修復欠損ではLETの違いによらず約2と一定だったのに対して、NHEJ修復欠損ではX線に比べて、HR修復欠損よりも高い値を示した。

論文

Nonhomologous end-joining repair plays a more important role than homologous recombination repair in defining radiosensitivity after exposure to high-LET radiation

高橋 昭久*; 久保 誠*; Ma, H.*; 中川 彰子*; 吉田 由香里*; 磯野 真由*; 金井 達明*; 大野 達也*; 古澤 佳也*; 舟山 知夫; et al.

Radiation Research, 182(3), p.338 - 344, 2014/09

 被引用回数:51 パーセンタイル:90.51(Biology)

DNA二本鎖切断(DSB)は相同組換え(HR)と非相同末端結合(NHEJ)により修復される。重粒子線治療における放射線増感剤の標的候補を明らかにすることを目的とした。がん抑制遺伝子p53欠損マウス胚線維芽細胞由来の野生型細胞, HR修復欠損細胞, NHEJ修復欠損細胞,二重修復欠損細胞を用いた。各細胞にX線,炭素線,鉄線,ネオン線,アルゴン線を照射し、コロニー形成法で生存率を調べた。10%生存率線量値(D10値)を用いて、増感比は(野生型細胞のD10値)/(修復欠損細胞のD10値)の式で算出した。D10値はいずれの線質においても、野生型細胞$$>$$HR修復欠損細胞$$>$$NHEJ修復欠損細胞$$>$$二重修復欠損細胞の順に低くなった。HR修復欠損による増感比はLET無関係に一定で約2であった。一方、NHEJ修復欠損の増感比はLETが高くなるに従い減少するものの、HR修復欠損よりも高い増感効果を示した。高LET放射線の高RBEの要因はNHEJ修復の抑制と誤修復であり、炭素線における増感剤の主要な標的候補はNHEJ修復であることが示唆された。

論文

Increase in cell motility by carbon ion irradiation via the Rho signaling pathway and its inhibition by the ROCK inhibitor Y-27632 in lung adenocarcinoma A549 cells

村田 和俊*; 野田 真永*; 尾池 貴洋*; 高橋 昭久*; 吉田 由香里*; 鈴木 義行*; 大野 達也*; 舟山 知夫; 小林 泰彦; 高橋 健夫*; et al.

Journal of Radiation Research, 55(4), p.658 - 664, 2014/07

 被引用回数:16 パーセンタイル:56.04(Biology)

ヒト肺がん細胞A549株のRhoシグナル伝達経路を介した遊走能に対し、炭素線照射が及ぼす影響を解析した。照射48時間経過後、炭素線照射したA549細胞の遊走能は大きくなり、遊走突起の形成も増加した。この遊走能の炭素線照射による増加は、X線照射後のそれと類似していた。ウェスタンブロット解析の結果は、照射した細胞がP-MLC2-S19タンパク質発現を増加させている一方で、MLC2タンパク質ファミリー全体の発現量に変化がないことを示した。ROCKタンパク質阻害剤であるY-27632の細胞への投与は、このP-MLC2-S19タンパク質の発現増加を抑制し、遊走能を低下させた。これらの結果より、ヒト肺がん細胞A549細胞への炭素線照射は、細胞遊走能をRhoシグナル伝達経路経由で増加させており、それはROCKタンパク質阻害剤で抑制されることが明らかとなった。

論文

Synergistic effect of heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin and X-rays, but not carbon-ion beams, on lethality in human oral squamous cell carcinoma cells

武者 篤*; 吉田 由香里*; 高橋 健夫*; 安藤 興一*; 舟山 知夫; 小林 泰彦; 根岸 明秀*; 横尾 聡*; 中野 隆史*

Journal of Radiation Research, 53(4), p.545 - 550, 2012/07

 被引用回数:9 パーセンタイル:45.24(Biology)

The purpose of this study is to clarify the effect of a heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in combination with X-rays or carbon-ion beams on cell killing in human oral squamous cell carcinoma LMF4 cells. Cell survival was measured by colony formation assay. Cell cycle distribution was analyzed by flow cytometry. Expression of DNA repair-related proteins was investigated by western blotting. The results showed 17-AAG having synergistic effects on cell lethality with X-rays, but not with carbon-ion beams. The 17-AAG decreased G$$_{2}$$/M arrest induced by X-rays, but not by carbon-ion beams. Both X-ray and carbon-ion irradiation up-regulated expression of non-homologous end-joining- associated proteins, Ku70 and Ku80, but 17-AAG inhibited only X-ray-induced up-regulation of Ku70 and Ku80. These results show that 17-AAG with X-rays releases G$$_{2}$$/M phase arrest and then cells carrying misrepaired DNA damage move to G$$_{1}$$ phase. We demonstrate, for the first time, that the radiosensitization effect of 17-AAG is not seen for carbon-ion beams because 17-AAG does not affect these changes.

論文

Evaluation of the relative biological effectiveness of carbon ion beams in the cerebellum using the rat organotypic slice culture system

吉田 由香里*; 鈴木 義行*; Al-Jahdari, W. S.*; 浜田 信行*; 舟山 知夫; 白井 克幸*; 加藤 弘之*; 坂下 哲哉; 小林 泰彦; 中野 隆史*

Journal of Radiation Research, 53(1), p.87 - 92, 2012/02

 被引用回数:8 パーセンタイル:42.05(Biology)

To clarify the relative biological effectiveness (RBE) values of carbon ion (C) beams in normal brain tissues, a rat organotypic slice culture system was used. The cerebellum was dissected from 10-day-old Wistar rats, cut parasagittally into approximately 600-$$mu$$m-thick slices and cultivated using a membrane-based culture system with a liquid-air interface. Slices were irradiated with 140 kV X-rays and 18.3 MeV/amu C-beams (linear energy transfer = 108 keV/$$mu$$m). After irradiation, the slices were evaluated histopathologically using hematoxylin and eosin staining, and apoptosis was quantified using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. Disorganization of the external granule cell layer (EGL) and apoptosis of the external granule cells (EGCs) were induced within 24 h after exposure to doses of more than 5 Gy from C-beams and X-rays. In the early postnatal cerebellum, morphological changes following exposure to C-beams were similar to those following exposure to X-rays. The RBEs values of C-beams using the EGL disorganization and the EGC TUNEL index endpoints ranged from 1.4 to 1.5. This system represents a useful model for assaying the biological effects of radiation on the brain, especially physiological and time-dependent phenomena.

論文

Radiation-induced ICAM-1 expression via TGF-$$beta$$1 pathway on human umbilical vein endothelial cells; Comparison between X-ray and carbon-ion beam irradiation

清原 浩樹*; 石崎 泰樹*; 鈴木 義行*; 加藤 弘之*; 浜田 信行*; 大野 達也*; 高橋 健夫*; 小林 泰彦; 中野 隆史*

Journal of Radiation Research, 52(3), p.287 - 292, 2011/03

 被引用回数:14 パーセンタイル:51.62(Biology)

Radiation-induced intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells was investigated with the use of an inhibitor of transforming growth factor-beta1 (TGF-$$beta$$1) receptor kinase (SB431542) and the effects of X-ray and carbon-ion beam were compared. Expression of ICAM-1 was increased by X-ray and carbon-ion beam irradiation and decreased significantly with SB431542 after both irradiations. The expression of ICAM-1 by 2 Gy of carbon-ion beam irradiation was 6.7 fold higher than that of non-irradiated cells, while 5 Gy of X-ray irradiation increased the expression of ICAM-1 by 2.5 fold. According to ICAM-1 expression, the effect of carbon-ion beam irradiation was about 2.2, 4.4 and 5.0 times greater than that of the same doses of X-ray irradiation (1, 2 and 5 Gy, respectively). The present results suggested that radiation-induced ICAM-1 expression on human umbilical vein endothelial cells (HUVE cells) was, at least partially, regulated by TGF-$$beta$$1. Carbon-ion beam induced significantly higher ICAM-1 expression than X-ray.

論文

Effectiveness of carbon-ion beams for apoptosis induction in rat primary immature hippocampal neurons

神沼 拓也*; 鈴木 義行*; 白井 克幸*; 水井 利幸*; 野田 真永*; 吉田 由香里*; 舟山 知夫; 高橋 健夫*; 小林 泰彦; 白尾 智明*; et al.

Journal of Radiation Research, 51(6), p.627 - 631, 2010/11

 被引用回数:9 パーセンタイル:33.95(Biology)

The direct biological effects of radiation, particularly accelerated heavy particle ions, on neurons are not fully known. Hence, the direct effect of carbon-ion beams on immature neurons was investigated by comparing to the effect of X-rays ${it in vitro}$ using primary hippocampal neurons. Primary neurons were prepared from hippocampi of fetal rats at embryonic day 18 from timed pregnant Wistar rats and cultured with Banker's methods. At 7 Days ${it In Vitro}$ (DIV), the cells were irradiated with 140 kV X-ray and 18.3 MeV/amu carbon-ion beams (LET = 108 keV/$$mu$$m). The cells were fixed with 4% paraformaldehyde at 12 hours after irradiation. Then, the cells were treated with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and DAPI staining for measuring the percentage of apoptosis (apoptotic index: AI). AI in sham-irradiated hippocampal neurons was 18%. The value of AI (AIs) of the cells irradiated with X-rays at 10 or 30 Gy were 15% or 23%, respectively. AI in cells irradiated with carbon-ion beams at 1 Gy, 3 Gy, 5 Gy and 10 Gy were 22%, 23%, 24% and 33%, respectively. AI was significantly increased by carbon-ion beams at 10 Gy (p $$<$$ 0.001). The apoptosis of hippocampal neurons increased in a dose-dependent manner following both X-ray and carbon-ion beams irradiation. Carbon-ion beams were about 10-fold more effective than X-rays for apoptosis induction in immature hippocampal neurons.

論文

Recent progress in the energy recovery linac project in Japan

坂中 章悟*; 明本 光生*; 青戸 智浩*; 荒川 大*; 浅岡 聖二*; 榎本 収志*; 福田 茂樹*; 古川 和朗*; 古屋 貴章*; 芳賀 開一*; et al.

Proceedings of 1st International Particle Accelerator Conference (IPAC '10) (Internet), p.2338 - 2340, 2010/05

日本においてERL型放射光源を共同研究チームで提案している。電子銃,超伝導加速空洞などの要素技術開発を進めている。また、ERL技術の実証のためのコンパクトERLの建設も進めている。これら日本におけるERL技術開発の現状について報告する。

論文

Electronic structure and magnetism of the diluted magnetic semiconductor Fe-doped ZnO nanoparticles

片岡 隆史*; 小林 正起*; 坂本 勇太*; Song, G. S.*; 藤森 淳*; Chang, F.-H.*; Lin, H.-J.*; Huang, D. J.*; Chen, C. T.*; 大河内 拓雄*; et al.

Journal of Applied Physics, 107(3), p.033718_1 - 033718_7, 2010/02

AA2009-0977.pdf:1.0MB

 被引用回数:53 パーセンタイル:85.88(Physics, Applied)

We have studied the electronic structure of Fe-doped ZnO nanoparticles, which have been reported to show ferromagnetism at room temperature, by X-ray photoemission spectroscopy (XPS), resonant photoemission spectroscopy (RPES), X-ray absorption spectroscopy (XAS) and X-ray magnetic circular dichroism (XMCD). From the experimental and cluster-model calculation results, we find that Fe atoms are predominantly in the Fe$$^{3+}$$ ionic state with mixture of a small amount of Fe$$^{2+}$$ and that Fe$$^{3+}$$ ions are dominant in the surface region of the nanoparticles. It is shown that the room temperature ferromagnetism in the Fe-doped ZnO nanoparticles is primarily originated from the antiferromagnetic coupling between unequal amounts of Fe$$^{3+}$$ ions occupying two sets of nonequivalent positions in the region of the XMCD probing depth of $$sim$$2-3 nm.

論文

Experimental observation of bulk band dispersions in the oxide semiconductor ZnO using soft X-ray angle-resolved photoemission spectroscopy

小林 正起*; Song, G.-S.*; 片岡 隆史*; 坂本 勇太*; 藤森 淳; 大河内 拓雄*; 竹田 幸治; 岡根 哲夫; 斎藤 祐児; 山上 浩志; et al.

Journal of Applied Physics, 105(12), p.122403_1 - 122403_4, 2009/06

BB2009-1947.pdf:0.84MB

 被引用回数:11 パーセンタイル:45.02(Physics, Applied)

ZnO is one of the most promising oxide semiconductors for applications to semiconductor electronics, especially for optical devices. Their inexpensiveness and environmental safety are also advantages for practical applications. The surface electronic structure of ZnO has been investigated so far using angle-resolved photoemission spectroscopy (ARPES) in the ultraviolet ray region (less than 150 eV), although those measurements are surface sensitive. Considering their potentiality of ZnO for extensive applications, it is desired to investigate the bulk electronic structure of ZnO experimentally. In this work, we have performed soft X-ray (SX) ARPES measurements on a ZnO thin film in order to probe the bulk electronic structure. All the obtained band dispersion reflects the hexagonal Brillouin zone of ZnO, indicating we succeeded in the observation of the band dispersion of ZnO by SX-ARPES.

論文

Heavy-ion-induced bystander killing of human lung cancer cells; Role of gap junctional intercellular communication

原田 耕作*; 野中 哲生*; 浜田 信行*; 桜井 英幸*; 長谷川 正俊*; 舟山 知夫; 柿崎 竹彦*; 小林 泰彦; 中野 隆史*

Cancer Science, 100(4), p.684 - 688, 2009/04

 被引用回数:54 パーセンタイル:75.81(Oncology)

The aim of the present study was to clarify the mechanisms of cell death induced by heavy-ion irradiation focusing on the bystander effect in human lung cancer A549 cells. In microbeam irradiation, each of 1, 5 and 25 cells under confluent cell conditions was irradiated with 1, 5 or 10 particles of energetic carbon ions, and then the surviving fraction of the population was measured by a clonogenic assay in order to investigate the bystander effect of heavy-ions. In this experiment, the limited number of cells (0.0001-0.002%, 5-25 cells) under confluent cell conditions irradiated with 5 or 10 carbon ions resulted in an exaggerated 8-14% increase in cell death by clonogenic assay. However, these overshooting responses were not observed under exponentially growing cell conditions. Furthermore, these responses were inhibited in cells treated with an inhibitor of gap junctional intercellular communication (GJIC), whereas these were markedly enhanced by the addition of a stimulator of GJIC. The present results suggest that bystander cell killing by heavy-ions was induced mainly by direct cell-to-cell communication, such as GJIC, which might play important roles in the bystander responses.

論文

Ceramide induces myogenic differentiation and apoptosis in ${it Drosophila}$ Schneider cells

河村 英将*; 立井 一明*; 野中 哲生*; 大日方 英*; 服部 友保*; 小川 愛*; 風間 秀子*; 浜田 信行*; 舟山 知夫; 坂下 哲哉; et al.

Journal of Radiation Research, 50(2), p.161 - 169, 2009/03

 被引用回数:7 パーセンタイル:27.07(Biology)

Cells exposed to genotoxic stress, such as ionizing radiation and DNA damaging reagents, either arrest the cell cycle to repair the genome, or undergo apoptosis, depending on the extent of the DNA damage. DNA damage also has been implicated in various differentiation processes. It has been reported that $$gamma$$-ray exposure or treatment with DNA-damaging agents could induce myogenic differentiation in ${it Drosophila}$ Schneider cells. However, the mechanism underlying this process has been poorly understood. In this study, exposure of Schneider cells to X-rays or energetic carbon ion beams caused increase of TUNEL-positive cells and conversion of round-shaped cells to elongated cells. Both upregulation of genes related to myogenesis and increase of myosin indicate that the radiation-induced morphological changes of Schneider cells were accompanied with myogenic differentiation. Because the intracellular ceramide was increased in Schneider cells after exposure to X-ray, we examined whether exogenous ceramide could mimic radiation-induced myogenic differentiation. Addition of membrane-permeable C$$_{2}$$-ceramide to Schneider cells increased apoptosis and expression of myogenic genes. These results suggest that ceramide plays important roles in both apoptosis and the radiation-induced myogenic differentiation process.

論文

Energetic heavy ions overcome tumor radioresistance caused by overexpression of Bcl-2

浜田 信行*; 原 孝光*; 大村 素子*; 舟山 知夫; 坂下 哲哉; 楚良 桜; 横田 裕一郎; 中野 隆史*; 小林 泰彦

Radiotherapy and Oncology, 89(2), p.231 - 236, 2008/11

 被引用回数:23 パーセンタイル:59.17(Oncology)

Overexpression of Bcl-2 is frequent in human cancers and has been associated with the radioresistance. Here we investigated the potential impact of heavy ions on Bcl-2 overexpressing tumors. Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) exposed to $$gamma$$-rays or heavy ions were assessed for the clonogenic survival, apoptosis and cell cycle distribution. Whereas Bcl-2 cells were more resistant to $$gamma$$-rays and helium ions (16.2 keV/$$mu$$m) than Neo cells, heavy ions (76.3-1610 keV/$$mu$$m) gave the comparable survival regardless of Bcl-2 overexpression. Carbon ions (108 keV/$$mu$$m) decreased the difference in the apoptotic incidence between Bcl-2 and Neo cells, and prolonged G$$_{2}$$/M arrest that occurred more extensively in Bcl-2 cells than in Neo cells. High-LET heavy ions overcome tumor radioresistance caused by Bcl-2 overexpression, which may be explained at least in part by the enhanced apoptotic response and prolonged G$$_{2}$$/M arrest. Thus, heavy-ion therapy may be a promising modality for Bcl-2 overexpressing radioresistant tumors.

論文

The Small-molecule Bcl-2 inhibitor HA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, to heavy-ion radiation

浜田 信行*; 片岡 啓子*; 楚良 桜*; 原 孝光*; 大村 素子*; 舟山 知夫; 坂下 哲哉; 中野 隆史*; 小林 泰彦

Radiotherapy and Oncology, 89(2), p.227 - 230, 2008/11

 被引用回数:9 パーセンタイル:31.78(Oncology)

This is the first study to demonstrate that the small-molecule Bcl-2 inhibitor HA14-1 renders human cervical cancer cells and their Bcl-2 over expressing radioresistant counterparts, but not normal fibroblasts, more susceptible to heavy ions. Thus, Bcl-2 may be an attractive target for improving the efficacy of heavy-ion therapy.

論文

A LET-dependent decrease in the apoptotic response of normal human fibroblast cultures to isosurvival doses of $$gamma$$-rays and energetic heavy ions

浜田 信行*; Ni, M.*; 舟山 知夫; 坂下 哲哉; 楚良 桜*; 中野 隆史*; 小林 泰彦

宇宙生物科学, 22(2), p.41 - 45, 2008/10

Biological effectiveness varies with the linear energy transfer (LET) of ionizing radiation. Plentiful evidence has been presented demonstrating that at physically equivalent doses, high-LET energetic heavy ions are more cytotoxic and genotoxic than low-LET photons like X-rays and $$gamma$$-rays. Notwithstanding, its potential impact at isosurvival doses is yet to be characterized. Here we investigated the cell-killing effectiveness of $$gamma$$-rays (0.2 keV/$$mu$$m) and five different beams of heavy ions with LET ranging from 16.2 to 1610 keV/$$mu$$m in confluent cultures of normal human fibroblasts. The relative biological effectiveness based on the dose giving 10% clonogenic survival peaked at 108 keV/$$mu$$m. In cultures exposed to the 10% survival doses, the yield of apoptotic cells escalated with time postirradiation but declined with LET. Our results imply that the cell death mode differs with LET at isosurvival levels.

論文

Heavy-ion microbeam irradiation induces bystander killing of human cells

浜田 信行*; 原 孝光*; 大村 素子*; Ni, M.*; 舟山 知夫; 坂下 哲哉; 楚良 桜*; 中野 隆史*; 小林 泰彦

宇宙生物科学, 22(2), p.46 - 53, 2008/10

Significant evidence indicates that ionizing radiation causes biological effects in nonirradiated bystander cells having received signals from directly irradiated cells. There is little information available hitherto as to the bystander effect of energetic heavy ions; however, our previous work has shown that in confluent cultures of normal human fibroblast AG01522 cells, targeted exposure of 0.0003% of cells to microbeams of 18.3 MeV/u $$^{12}$$C (103 keV/$$mu$$m) and 13.0 MeV/u $$^{20}$$Ne (375 keV/$$mu$$m) ions can similarly cause almost 10% decreases in the clonogenic survival, and twofold increments in the incidence of apoptosis whose temporal kinetics varies between irradiated and bystander cells. Using this experimental system, here we further report that bystander responses of AG01522 cells to 17.5 MeV/u 20Ne ions (294 keV/$$mu$$m) are consistent with those to 18.3 MeV/u $$^{12}$$C and 13.0 MeV/u $$^{20}$$Ne ions. We also demonstrate that such bystander-induced reductions in the survival are less pronounced and occur independently of Bcl-2 overexpression in human cervical cancer HeLa cells.

論文

Exposure of normal human fibroblasts to heavy-ion radiation promotes their morphological differentiation

楚良 桜*; 浜田 信行*; 原 孝光*; 舟山 知夫; 坂下 哲哉; 横田 裕一郎; 中野 隆史*; 小林 泰彦

宇宙生物科学, 22(2), p.54 - 58, 2008/10

Here we investigated the potential impact of energetic heavy ions on fibroblast differentiation. The differentiation pattern was morphologically determined at days 3 and 5 after exposure to graded dose of $$gamma$$-rays (0.2 keV/$$mu$$m) or carbon ions (18.3 MeV/u, 108 keV/$$mu$$m). The cells irradiated with higher doses progressed toward later differentiation stages as time goes postirradiation, but underwent fewer cell divisions. Thus, radiation exposure accelerated morphological differentiation, for which carbon ions were more effective than $$gamma$$-rays. The relative biological effectiveness of carbon ions for differentiation was higher than that for the clonogenic survival, and this was the most case for terminally differentiated cells that may not divide any more. The results are suggestive of the distinct mechanism underlying inactivation of clonogenic potential between radiation qualities, such that the contribution of the differentiation to heavy ion-induced reductions in the survival is greater than to those induced by photons. Such accelerated differentiation could be a protective mechanism that minimizes further expansion of aberrant cells.

論文

The Survival of heavy ion-irradiated Bcl-2 overexpressing radioresistant tumor cells and their progeny

浜田 信行*; 原 孝光*; 大村 素子*; 舟山 知夫; 坂下 哲哉; 楚良 桜*; 中野 隆史*; 小林 泰彦

Cancer Letters, 268(1), p.76 - 81, 2008/09

 被引用回数:10 パーセンタイル:23.48(Oncology)

Here, we investigated the cell killing effectiveness of heavy-ion radiation in Bcl-2 overexpressing radioresistant tumor cells. First, irradiated cells underwent primary colony formation. Radioresistance decreased with increasing linear energy transfer (LET), indicating that heavy ions may be a promising therapeutic modality for Bcl-2 overexpressing tumors. Second, cells in primary colonies were reseeded for secondary colony formation. The incidence of delayed reproductive death increased with LET irrespective of Bcl-2 overexpression, suggesting that Bcl-2 overexpression may not facilitate heavy ion induced genomic instability.

論文

Proliferation and cell death of human glioblastoma cells after carbon-ion beam exposure; Morphologic and morphometric analyses

大石 琢磨*; 佐々木 惇*; 浜田 信行*; 石内 勝吾*; 舟山 知夫; 坂下 哲哉; 小林 泰彦; 中野 隆史*; 中里 洋一*

Neuropathology, 28(4), p.408 - 416, 2008/08

 被引用回数:14 パーセンタイル:46.78(Clinical Neurology)

Using CGNH-89 cells exposed to 0-10 Gy of X-ray (140 kVp) or carbon-ions (18.3 MeV/nucleon, LET = 108 keV/$$mu$$m), we performed conventional histology and immunocytochemistry with MIB-1 antibody, transmission electron microscopy, and computer-assisted, nuclear size measurements. After carbon-ion and X-ray exposure, living cells showed decreased cell number, nuclear condensation, increased atypical mitotic figures, and a tendency of cytoplasmic enlargement at the level of light microscopy. The deviation of the nuclear area size increased during 48 hours after irradiation, while the small cell fraction increased in 336 hours. In glioblastoma cells of the control, 5 Gy carbon-beam, and 10 Gy carbon-beam, and MIB-1 labeling index decreased in 24 hours but increased in 48 hours. Ultrastructurally, cellular enlargement seemed to depend on vacuolation, swelling of mitochondria, and increase of cellular organelles, such as the cytoskeleton and secondary lysosome. We could not observe apoptotic bodies in the CGNH-89 cells under any conditions. We conclude that carbon-ion irradiation induced cell death and senescence in a glioblastoma cell line with mutant TP53. Our results indicated that the increase of large cells with enlarged and bizarre nuclei, swollen mitochondria, and secondary lysosome occurred in glioblastoma cells after carbon-beam exposure.

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