Bystander cellular effects induced by low-fluence charged particles

低通量带电粒子引起的旁观者细胞效应

• 批准号: 16510052
• 负责人: SUZUKI Masao
• 金额: $ 2.37万
• 依托单位: National Institute of Radiological Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16510052/
• 关键词: bystander effects; normal human skin fibroblasts; colony formation; reproductive cell death; hprt locus; mutation; carbon-ion beams; cell-cell communication; 重粒子線; 突然変異誘発効果; 高LET重粒子線; クロマチン切断誘発効果; 早期染色体凝縮(PCC)法

We have investigated bystander cellular responses in normal human fibroblasts irradiated with low-fluence ion-beams of low-energy carbon ions. Irradiation dishes were constructed by drilling 6.5mm holes in the center of 35mm-diameter tissue culture dishes and attaching a 2.5μm-thick Mylar film over the bottom of the hole to provide a window for low-energy carbon ion beams. Cells were inoculated onto the Mylar film in the dishes and then irradiated with 6MeV/n carbon ions at a fluence of 2 x 10^5 particles/cm^2. The beam was generated by the Medium Energy Beam Course at the Heavy Ion Medical Accelerator in Chiba (HIMAC). Cells were exposed using 4 different protocols ; (1)Cells were irradiated with all of the cells on the Mylar film ;. (2)Cells were irradiated with half of the cell population on the Mylar film ; (3)Irradiated cells and un-irradiated control cells were pooled in a 1:1 ratio and plated as a single culture ; and (4)Half of the cells were irradiated and treated with a specific inhibitor of gap junction mediated cell-cell communication (40μM lindane). Cell killing, which was assayed with a colony formation assay, showed that the surviving fraction of the irradiated group (2)was almost the same as for group (1).In addition, a similar level of survival was seen in the group (4)and in the mixed population group (3).Mutation induction, which was scored as the number of 6-thioguanine resistant clones arising at the HPRT locus, showed the same trend as the cell killing effect. Thus there is evidence that the bystander effect for both cell killing and mutation induction occurred in the un-irradiated half of the cells in group (2). Since lindane apparently inhibited these effects, this suggests that gap junction mediated cell-cell communication may play an important role in the induction of the bystander effect.

我们研究了低能碳离子的低通量离子束照射下的正常人成纤维细胞的旁观者细胞反应。在直径35 mm的组织培养皿中央钻6.5 mm的孔，在孔的底部贴上2.5μm厚的聚乳酸薄膜，为低能碳离子束提供窗口。将细胞接种到培养皿中的Mylar膜上，然后用6 MeV/n的碳离子以2×105粒子/cm^2的剂量进行照射。束流由千叶重离子医疗加速器(HIMAC)的中能束课程产生。用4种不同的方法暴露细胞：(1)用Mylar膜上的所有细胞照射细胞；(2)用Mylar膜上一半的细胞群进行照射；(3)将照射后的细胞和未照射的对照细胞按1：1的比例混合，作为单一培养细胞；(4)照射后用缝隙连接介导的细胞-细胞通讯的特异性抑制剂(40μM lindane)处理一半的细胞。细胞杀伤实验表明，照射组(2)的存活分数与照射组(1)几乎相同。此外，照射组(4)和混合种群组(3)的存活水平相似。以HPRT基因座出现的6-硫代鸟嘌呤抗性克隆数为指标的突变诱导率与细胞杀伤效应的趋势相同。因此，有证据表明，组(2)中未照射的一半细胞发生了旁观者效应，对细胞的杀伤和突变诱导都是如此。由于林丹明显抑制了这些效应，这表明缝隙连接介导的细胞-细胞通讯可能在旁观者效应的诱导中发挥重要作用。

项目成果

Effect of medium on chromatin damage in bystander mammalian cells.

培养基对旁观者哺乳动物细胞染色质损伤的影响。

• DOI: 10.1667/rr3226
• 发表时间: 2004
• 期刊: Radiation research
• 影响因子: 3.4
• 作者: Suzuki,Masao;Zhou,Hongning;Geard,CharlesR;Hei,TomK
• 通讯作者: Hei,TomK

宇宙からヒトを眺めて-宇宙放射線の人体への影響-

从太空看人类——宇宙辐射对人体的影响——

• 发表时间: 2004
• 作者: 稲吉哲弥;河辺伸二;池田哲夫;王大鵬;松並良;(社)レーザー学会編纂;藤高和信 他
• 通讯作者: 藤高和信 他

マイクロビームを利用した研究、宇宙からヒトを眺めて:宇宙放射線の人体への影響

使用微束进行研究，从太空观察人类：宇宙辐射对人体的影响

• 发表时间: 2004
• 作者: Yukawa;O et al.;鈴木政雄
• 通讯作者: 鈴木政雄

Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions

• DOI: 10.1016/j.mrfmmm.2005.08.007
• 发表时间: 2006-02-22
• 期刊: MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
• 影响因子: 2.3
• 作者: Suzuki, M;Tsuruoka, C;Watanabe, M
• 通讯作者: Watanabe, M

Reduction in life span on normal human fibroblasts exposed to very low-dose rate charged particles.

暴露于极低剂量率带电粒子的正常人类成纤维细胞的寿命会缩短。

• 发表时间: 2005
• 期刊: Radiation Research 164
• 作者: M.Suzuki;et al.
• 通讯作者: et al.