Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, PR China; University of Science and Technology of China, Hefei 230026, PR China.
Biophysics Group, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, PR China.
DNA Repair (Amst). 2018 Mar;63:39-46. doi: 10.1016/j.dnarep.2018.01.009. Epub 2018 Feb 1.
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.
重离子辐射因其在其轨迹上的能量沉积变化和高细胞杀伤效应而引起广泛关注，被认为是一种有效的癌症治疗方法。生殖细胞死亡（RCD），也称为克隆死亡，是放射治疗后癌细胞死亡的一种重要方式。虽然已经通过体外克隆形成测定法证明了各种线性能量转移的重离子照射诱导的 RCD，但对于整个生物体范围内重离子照射的 RCD 分布知之甚少。在这项研究中，首次使用秀丽隐杆线虫的生殖腺组织模型来评估体内碳离子照射诱导的 RCD。设计了聚甲基丙烯酸甲酯楔形物，以提供逐渐变化的屏蔽厚度，从而使线虫能够暴露于整个碳离子照射范围内。碳离子照射以剂量依赖性方式在整个范围内导致 RCD 的显著诱导。生物峰与物理布拉格峰不对应，而是随着辐射剂量的增加向前移动，而不是向前扩展。RCD 的分布范围的程度和形状也受到线虫发育阶段的影响。与野生型线虫相比，DNA 损伤检查点的基因突变不会影响处于生物峰位置的突变型线虫的反应，但会降低入口区域的放射敏感性。同源重组（HR）受损的线虫中观察到 RCD 的诱导增加，但非同源末端连接途径的线虫中没有观察到，这表明 HR 修复在秀丽隐杆线虫生殖腺细胞中对处理碳离子诱导的 DNA 损伤至关重要。这些体内对碳离子照射的 RCD 的独特表现可能为进一步研究重离子照射的生物学效应提供新的线索。
