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低能量密度离子束照射下正常人成纤维细胞的旁观者细胞反应。通过在直径 35mm 的组织培养皿中心钻 6.5mm 的孔并在孔的底部贴上 2.5μm 厚的聚酯薄膜来构建照射皿，为低能碳离子束提供窗口。将细胞接种到培养皿中的聚酯薄膜上，然后用 6MeV/n 碳离子以 2 x 10^5 颗粒/cm^2 的注量进行照射。该束是由千叶重离子医疗加速器 (HIMAC) 的中能束课程产生的。使用 4 种不同的方案暴露细胞； (1)对Mylar薄膜上的所有细胞进行照射；。 (2)用Mylar薄膜上一半细胞群照射细胞； (3)将照射的细胞和未照射的对照细胞以1:1的比例混合并作为单一培养物铺板； (4)对一半细胞进行照射，并用间隙连接介导的细胞间通讯的特异性抑制剂(40μM林丹)处理。通过集落形成测定法进行的细胞杀伤显示，照射组(2)的存活分数与组(1)几乎相同。此外，组(4)和混合群组(3)中也观察到类似的存活水平。突变诱导(以HPRT位点处出现的6-硫鸟嘌呤抗性克隆的数量来评分)显示出与细胞杀伤效果相同的趋势。因此，有证据表明，细胞杀伤和突变诱导的旁观者效应发生在组（2）中未受照射的一半细胞中。由于林丹明显抑制了这些效应，这表明间隙连接介导的细胞间通讯可能在诱导旁观者效应中发挥重要作用。

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

LET and Ion Species Dependence for Cell Killing in Normal Human Skin Fibroblasts

• DOI: 10.1667/rr3360
• 发表时间: 2005-05
• 作者: C. Tsuruoka;Masao Suzuki;T. Kanai;K. Fujitaka

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