Sridharan D M, Asaithamby A, Bailey S M, Costes S V, Doetsch P W, Dynan W S, Kronenberg A, Rithidech K N, Saha J, Snijders A M, Werner E, Wiese C, Cucinotta F A, Pluth J M
a Lawrence Berkeley National Laboratory, Berkeley, California.
Radiat Res. 2015 Jan;183(1):1-26. doi: 10.1667/RR13804.1. Epub 2015 Jan 7.
During space travel astronauts are exposed to a variety of radiations, including galactic cosmic rays composed of high-energy protons and high-energy charged (HZE) nuclei, and solar particle events containing low- to medium-energy protons. Risks from these exposures include carcinogenesis, central nervous system damage and degenerative tissue effects. Currently, career radiation limits are based on estimates of fatal cancer risks calculated using a model that incorporates human epidemiological data from exposed populations, estimates of relative biological effectiveness and dose-response data from relevant mammalian experimental models. A major goal of space radiation risk assessment is to link mechanistic data from biological studies at NASA Space Radiation Laboratory and other particle accelerators with risk models. Early phenotypes of HZE exposure, such as the induction of reactive oxygen species, DNA damage signaling and inflammation, are sensitive to HZE damage complexity. This review summarizes our current understanding of critical areas within the DNA damage and oxidative stress arena and provides insight into their mechanistic interdependence and their usefulness in accurately modeling cancer and other risks in astronauts exposed to space radiation. Our ultimate goals are to examine potential links and crosstalk between early response modules activated by charged particle exposure, to identify critical areas that require further research and to use these data to reduced uncertainties in modeling cancer risk for astronauts. A clearer understanding of the links between early mechanistic aspects of high-LET response and later surrogate cancer end points could reveal key nodes that can be therapeutically targeted to mitigate the health effects from charged particle exposures.
在太空旅行期间，宇航员会受到多种辐射，包括由高能质子和高能带电（HZE）核组成的银河宇宙射线，以及含有低至中能质子的太阳粒子事件。这些辐射暴露带来的风险包括致癌作用、中枢神经系统损伤和组织退行性影响。目前，职业辐射限值基于使用一个模型计算出的致命癌症风险估计值，该模型纳入了来自受辐射人群的人类流行病学数据、相对生物效应估计值以及来自相关哺乳动物实验模型的剂量反应数据。太空辐射风险评估的一个主要目标是将美国国家航空航天局空间辐射实验室和其他粒子加速器的生物学研究中的机制数据与风险模型联系起来。HZE暴露的早期表型，如活性氧的诱导、DNA损伤信号传导和炎症，对HZE损伤的复杂性很敏感。本综述总结了我们目前对DNA损伤和氧化应激领域关键区域的理解，并深入探讨了它们的机制相互依存关系以及在准确模拟暴露于太空辐射的宇航员患癌症和其他风险方面的有用性。我们的最终目标是研究带电粒子暴露激活的早期反应模块之间的潜在联系和相互作用，确定需要进一步研究的关键领域，并利用这些数据减少模拟宇航员癌症风险时的不确定性。更清楚地了解高传能线密度反应的早期机制方面与后期替代癌症终点之间的联系，可能会揭示出可以作为治疗靶点的关键节点，以减轻带电粒子暴露对健康的影响。
