Wang Xiang, Farris Iii Alton B, Wang Ping, Zhang Xiangming, Wang Hongyan, Wang Ya
a Department of Radiation Oncology, School of Medicine and the Winship Cancer Institute of Emory University, Atlanta, Georgia 30322.
Radiat Res. 2015 Feb;183(2):233-9. doi: 10.1667/RR13884.1. Epub 2015 Jan 30.
Space radiation, which is comprised of high-energy charged (HZE) particles with different high-linear energy transfer (LET), induces more severe biological effects than the Earth's radiation. NASA has mandated that risk estimates of carcinogenesis induced by exposure to HZE particles with different LET be determined before conducting human explorations of Mars. Because lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in humans, it is critical the risk of that radiation-induced lung tumorigenesis be included when estimating the risks of space radiation to astronauts. To address this, we examined the incidence of lung tumorigenesis in wild-type C57BL/6 mice at 1.5 years after 1 Gy exposure (single or fractionated dose) to different types of radiation with different LET (iron, silicon, oxygen and X ray). We chose wild-type mice for this study because previous studies of radiation-induced lung tumorigenesis using mutant mice models (either downregulated tumor suppressors or upregulated oncogenes) may not accurately reflect the response of healthy individuals (astronauts) to space radiation. Our study clearly showed that HZE particles (iron, silicon and oxygen) induced a higher incidence of lung tumorigenesis than X rays, and that their relative effectiveness at 1 Gy was >6. In addition, we found that silicon exposure appears to induce more aggressive lung tumors. These results provide valuable information for future followup experiments to study the underlying mechanism of lung tumorigenesis, which will improve risk estimation of space radiation-induced lung tumorigenesis and help in the development of mitigators to reduce risk if it exceeds NASA guidelines.
空间辐射由具有不同高线性能量传递（LET）的高能带电（HZE）粒子组成，与地球辐射相比，会引发更严重的生物效应。美国国家航空航天局（NASA）已下令，在开展火星载人探索之前，要确定暴露于不同LET的HZE粒子所诱发的致癌风险评估。由于肺癌是人类最常被诊断出的癌症，也是癌症死亡的主要原因，因此在估计空间辐射对宇航员的风险时，纳入辐射诱发肺肿瘤发生的风险至关重要。为解决这一问题，我们研究了野生型C57BL/6小鼠在接受1 Gy不同类型、不同LET（铁、硅、氧和X射线）辐射（单次或分次剂量）1.5年后肺肿瘤发生的发生率。我们选择野生型小鼠进行这项研究，因为之前使用突变小鼠模型（肿瘤抑制因子下调或癌基因上调）进行的辐射诱发肺肿瘤发生的研究可能无法准确反映健康个体（宇航员）对空间辐射的反应。我们的研究清楚地表明，HZE粒子（铁、硅和氧）诱发肺肿瘤发生的发生率高于X射线，并且它们在1 Gy时的相对效能>6。此外，我们发现硅暴露似乎会诱发更具侵袭性的肺肿瘤。这些结果为未来后续实验提供了有价值的信息，以研究肺肿瘤发生的潜在机制，这将改善对空间辐射诱发肺肿瘤发生的风险估计，并有助于开发缓解措施，以便在风险超过NASA指导方针时降低风险。
