Study of effect of ionizing radiation on germline cells

电离辐射对生殖细胞影响的研究

• 批准号: 16310033
• 负责人: HIGASHITANI Atsushi
• 金额: $ 10.61万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16310033/
• 关键词: apoptosis; cell cycle; mitochondria; checkpoint; DNA damage; ionizing radiation; bystander effect; strong magnetic field; G1停止; 生殖; 減数分裂; 重イオン線; マイクロビーム

To investigate positional effects of radiation with an energetic heavy-ion microbeam on germline cells using an experimental model metazoan Caenorhabditis elegans. The germline cells were irradiated with raster-scanned broad beam or collimated microbeam of 220MeV 12C5t particles delivered from the azimuthally varying field (AVF) cyclotron, and subsequently observed for cell cycle arrest and apoptosis. Whole-body irradiation with the broad beam at the L4 larval stage arrested germ cell proliferation. When the tip region of the gonad arm was irradiated locally with the microbeam at the L4 stage, the same arrest was observed. When the microbeams were used to irradiate the pachytene region of the gonad arm, at a young gravid stage, radiation-induced apoptosis occurred in the gonad. In contrast, arrest and apoptosis were not induced in the non-irradiated neighboring region or the opposite gonad. Similar results were confirmed in the c-abl-1 (mammalian ortholog of cellular counterpart of Abelson murine leukemia virus) mutant that is hypersensitive to radiation-induced apoptosis. In addition, we demonstrated that several genes encoding apoptotic cell-death activators and secreted surface proteins were upregulated after ionizing radiation. Some of them were also upregulated by defect of mitochondrial DNA replication. These results indicate that the microbeam irradiation is useful in characterizing tissue-specific, local biological response to radiation in organisms. DNA damage-induced cell cycle arrest and apoptosis were observed in locally irradiated regions, but there was little, if any, ''bystander effect'' in the nematode.

使用实验模型后生动物秀丽隐杆线虫研究高能重离子微束辐射对生殖细胞的位置影响。用方位变场 (AVF) 回旋加速器传递的 220MeV 12C5t 粒子的光栅扫描宽光束或准直微束照射生殖细胞，随后观察细胞周期停滞和细胞凋亡。在 L4 幼虫阶段用宽光束进行全身照射可抑制生殖细胞增殖。当在L4阶段用微束局部照射性腺臂的尖端区域时，观察到相同的停滞。当微束用于照射性腺臂的粗线期区域时，在年轻妊娠阶段，性腺中发生了辐射诱导的细胞凋亡。相反，在未受辐射的邻近区域或相对的性腺中没有诱导停滞和细胞凋亡。在对辐射诱导的细胞凋亡高度敏感的 c-abl-1（Abelson 鼠白血病病毒的细胞对应物的哺乳动物直系同源物）突变体中也证实了类似的结果。此外，我们证明了编码凋亡细胞死亡激活剂和分泌表面蛋白的几个基因在电离辐射后上调。其中一些还因线粒体 DNA 复制缺陷而上调。这些结果表明，微束照射可用于表征生物体对辐射的组织特异性、局部生物反应。在局部照射区域观察到 DNA 损伤诱导的细胞周期停滞和细胞凋亡，但在线虫中几乎没有“旁观者效应”（如果有的话）。