Cao Qianlin, Liu Wei, Wang Jingdong, Cao Jianping, Yang Hongying
School of Radiation Medicine and Protection, Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, 199 Renai Road, Suzhou Industrial Park, Suzhou, 215123, Jiangsu, People's Republic of China.
Department of Radiotherapy and Oncology, Second Affiliated Hospital, Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu, People's Republic of China.
Radiat Environ Biophys. 2018 Mar;57(1):31-40. doi: 10.1007/s00411-017-0719-0. Epub 2017 Nov 10.
Space radiation cancer risk may be a potential obstacle for long-duration spaceflight. Among all types of cancer space radiation may induce, lung cancer has been estimated to be the largest potential risk. Although previous animal study has shown that Fe ions, the most important contributor to the total dose equivalent of space radiation, induced a higher incidence of lung tumorigenesis per dose than X-rays, the underlying mechanisms at cellular level remained unclear. Therefore, in the present study, we investigated long-term biological changes in NL20 human bronchial epithelial cells after exposure to Fe ion or X-ray irradiation. We found that compared with sham control, the progeny of NL20 cells irradiated with 0.1 Gy of Fe ions showed slightly increased micronucleus formation, significantly decreased cell proliferation, disturbed cell cycle distribution, and obviously elevated intracellular ROS levels accompanied by reduced SOD1 and SOD2 expression, but the progeny of NL20 cells irradiated with 0.9 Gy of X-rays did not show any significant changes. More importantly, Fe ion exposure caused much greater soft-agar colony formation than X-rays did in the progeny of irradiated NL20 cells, clearly suggesting higher cell transformation potential of Fe ions compared with X-rays. These data may shed the light on the potential lung tumorigenesis risk from Fe ion exposure. In addition, ATM inhibition by Ku55933 reversed some of the changes in the progeny of Fe ion-irradiated cells but not others such as soft-agar colony formation, suggesting complex processes from DNA damage to carcinogenesis. These data indicate that even a single low dose of Fe ions can induce long-term biological responses such as cell transformation, etc., suggesting unignorable health risk from space radiation to astronauts.
太空辐射致癌风险可能是长期太空飞行的一个潜在障碍。在太空辐射可能诱发的所有癌症类型中,肺癌被估计是最大的潜在风险。尽管先前的动物研究表明,太空辐射总剂量当量的最重要贡献者铁离子,每剂量诱发肺肿瘤发生的发生率高于X射线,但细胞水平的潜在机制仍不清楚。因此,在本研究中,我们调查了NL20人支气管上皮细胞在暴露于铁离子或X射线照射后的长期生物学变化。我们发现,与假对照相比,用0.1 Gy铁离子照射的NL20细胞后代显示微核形成略有增加,细胞增殖显著降低,细胞周期分布紊乱,细胞内ROS水平明显升高,同时SOD1和SOD2表达降低,但用0.9 Gy X射线照射的NL20细胞后代未显示任何显著变化。更重要的是,在照射后的NL20细胞后代中,铁离子暴露比X射线导致更大的软琼脂集落形成,这清楚地表明铁离子与X射线相比具有更高的细胞转化潜力。这些数据可能揭示了铁离子暴露导致潜在肺肿瘤发生风险的情况。此外,Ku55933对ATM的抑制作用逆转了铁离子照射细胞后代中的一些变化,但没有逆转其他变化,如软琼脂集落形成,这表明从DNA损伤到致癌的过程很复杂。这些数据表明,即使是单次低剂量的铁离子也能诱导细胞转化等长期生物学反应,这表明太空辐射对宇航员的健康风险不可忽视。