Induction of reproductive cell death in Caenorhabditis elegans across entire linear-energy-transfer range of carbon-ion irradiation
Induction of reproductive cell death in Caenorhabditis elegans across entire linear-energy-transfer range of carbon-ion irradiation
复制标题
在碳离子辐射的整个线性能量转移范围内诱导秀丽隐杆线虫生殖细胞死亡
DOI：
10.1016/j.dnarep.2018.01.009
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发表时间：
2018-03-01
期刊：
影响因子：
3.8
通讯作者：
Bian, Po
中科院分区：
文献类型：
--
作者：
Chen, Liangwen;Tang, Huangqi;Bian, Po
重离子辐射作为一种有效的肿瘤治疗方法，由于其沿着轨迹能量沉积的变化和高的细胞杀伤效应而引起广泛关注。生殖细胞死亡（reproductive cell death，RCD），又称克隆性死亡，是放射治疗后肿瘤细胞死亡的一种重要方式。虽然重离子辐照诱导的RCD与各种线性能量转移已被证明使用克隆形成试验在体外，很少有人知道的RCD的分布范围内的重离子辐照在整个生物体的水平。在这项研究中，秀丽隐杆线虫外阴组织模型首次被用来评估RCD在体内由碳离子辐射诱导。一个聚甲基丙烯酸甲酯楔形物被设计成提供逐渐变化的屏蔽厚度，这样蠕虫就可以暴露在整个范围的碳离子辐射中。碳离子辐照导致在整个范围内以剂量依赖性方式显著诱导RCD。生物峰不对应于物理布拉格峰，并且随着辐射剂量的增加而向前移动，而不是向前扩展。RCD的范围分布程度和形状也受到蠕虫发育阶段的影响。与野生型蠕虫相比，DNA损伤检查点中的基因突变不影响位于生物峰的突变蠕虫的反应，但降低了入口区域的放射敏感性。在同源重组（HR）受损的蠕虫中观察到RCD的诱导增加，但在非同源末端连接途径中没有观察到，这表明HR修复在C. elegans在处理碳离子诱导的DNA损伤方面的作用。这些在体内对碳离子辐射反应的独特表现可能为进一步研究重离子辐射的生物学效应提供新的线索。
Heavy-ion radiation has attracted extensive attention as an effective cancer therapy because of the varying energy deposition along its track and its high cell-killing effect. Reproductive cell death (RCD), also known as clonogenic death, is an important mode of death of the cancer cells after radiotherapy. Although RCD induced by heavy-ion irradiation with various linear energy transfers has been demonstrated using clonogenic assay in vitro, little is known about the distribution of RCD across the range of heavy-ion irradiation at the level of whole organisms. In this study, a vulval tissue model of Caenorhabditis elegans was for the first time used to assess RCD in vivo induced by carbon-ion irradiation. A polymethyl methacrylate wedge was designed to provide a gradually varying thickness of shielding, so worms could be exposed to the entire range of carbon-ion irradiation. The carbon-ion irradiation led to a significant induction of RCD over the entire range in a dose-dependent manner. The biological peak did not correspond to the physical Bragg peak and moved forward, rather than spread forward, as radiation dose increased. The degree and shape of the range-distribution of RCD were also affected by the developmental stages of the worms. The gene mutations in DNA-damage checkpoints did not affect the responses of mutant worms positioned in biological peaks, compared to wild-type worms, but decreased radio sensitivity in the entrance region. An increased induction of RCD was observed in the worms impaired in homologous recombination (HR), but not in non-homologous end jointing pathway, suggesting a crucial role of HR repair in vulval cells of C. elegans in dealing with the carbon-ion-induced DNA damage. These unique manifestations of RCD in vivo in response to carbon-ion irradiation might provide new clues for further investigating the biological effects of heavy-ion irradiation.