Biological Characterization of Low-Energy Ions with High-Energy Deposition on Human Cells

Biological Characterization of Low-Energy Ions with High-Energy Deposition on Human Cells
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低能离子在人体细胞上的高能沉积的生物学表征

DOI:
10.1667/rr13747.1
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发表时间:
2014
影响因子:
3.8
通讯作者:
F. Cucinotta
F. Cucinotta
中科院分区:
医学2区
文献类型:
--
作者:
Janapriya Saha;P. Wilson;P. Thieberger;D. Lowenstein;Minli Wang;F. Cucinotta

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在太空旅行中,宇航员暴露在由高能核粒子组成的宇宙辐射中。癌症患者在接受质子和碳束治疗时也会暴露在高能核粒子中。穿过屏蔽材料和组织的高能粒子的核相互作用产生高LET的低能(<10 MeV/n)次级粒子,这些次级粒子对总辐射照射量有很大贡献。径迹结构理论表明,高电荷和能量(HZE)粒子和低能二次离子类似的LET将有不同的生物效应的细胞和组织损伤的终点。我们研究了利用布鲁克海文国家实验室(BNL)的串联货车德格拉夫加速器的高LET的低能量离子的生物效应,并将这些与HZE粒子的实验进行了比较,该实验模拟了在BNL的NASA空间辐射实验室(NSRL)产生的空间环境。用5.6MeV/n硼(LET 205 keV/μm)、5.3MeV/n硅(LET 1241 keV/μm)、600 MeV/n铁(LET 180 keV/μm)和77 MeV/n氧(LET 58 keV/μm)粒子照射后,进行DNA损伤反应蛋白的免疫染色。低能量离子造成更多的持久性DNA损伤反应(DDR)蛋白灶照射人成纤维细胞和食管上皮细胞相比,HZE粒子。更详细的研究比较硼离子铁粒子,表明硼离子辐射导致更强的G2延迟相比,铁粒子曝光,硼离子也显示了早期招募Rad 51在双链断裂(DSB)网站,这表明在低能量,但高LET粒子的DSB修复的同源重组的偏好。我们的实验表明,非常高的能量辐射沉积的低能量离子,银河宇宙辐射和太阳粒子事件二次辐射的代表,产生大量的,但局部的DNA损伤,导致延迟DSB修复,和不同的细胞反应,从HZE粒子。因此,低能重离子为研究辐射反应中的同源重组修复提供了一个有价值的探针。
During space travel, astronauts are exposed to cosmic radiation that is comprised of high-energy nuclear particles. Cancer patients are also exposed to high-energy nuclear particles when treated with proton and carbon beams. Nuclear interactions from high-energy particles traversing shielding materials and tissue produce low-energy (<10 MeV/n) secondary particles of high-LET that contribute significantly to overall radiation exposures. Track structure theories suggest that high charge and energy (HZE) particles and low-energy secondary ions of similar LET will have distinct biological effects for cellular and tissue damage endpoints. We investigated the biological effects of low-energy ions of high LET utilizing the Tandem Van de Graaff accelerator at the Brookhaven National Laboratory (BNL), and compared these to experiments with HZE particles, that mimic the space environment produced at NASA Space Radiation Laboratory (NSRL) at BNL. Immunostaining for DNA damage response proteins was carried out after irradiation with 5.6 MeV/n boron (LET 205 keV/μm), 5.3 MeV/n silicon (LET 1241 keV/μm), 600 MeV/n Fe (LET 180 keV/μm) and 77 MeV/n oxygen (LET 58 keV/μm) particles. Low-energy ions caused more persistent DNA damage response (DDR) protein foci in irradiated human fibroblasts and esophageal epithelial cells compared to HZE particles. More detailed studies comparing boron ions to Fe particles, showed that boron-ion radiation resulted in a stronger G2 delay compared to Fe-particle exposure, and boron ions also showed an early recruitment of Rad51 at double-strand break (DSB) sites, which suggests a preference of homologous recombination for DSB repair in low-energy albeit high-LET particles. Our experiments suggest that the very high-energy radiation deposition by low-energy ions, representative of galactic cosmic radiation and solar particle event secondary radiation, generates massive but localized DNA damage leading to delayed DSB repair, and distinct cellular responses from HZE particles. Thus, low-energy heavy ions provide a valuable probe for studies of homologous recombination repair in radiation responses.
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