Finkelstein Sophie R, Patel Rutulkumar, Deland Katherine, Mercer Joshua, Starr Bryce, Zhu Daniel, Min Hooney, Reinsvold Michael, Campos Lorraine Da Silva, Williams Nerissa, Luo Lixia, Ma Yan, Neff Jadee, Hoenerhoff Mark, Moding Everett J, Kirsch David G
bioRxiv. 2023 Jun 8:2023.06.06.543754. doi: 10.1101/2023.06.06.543754.
The main deterrent to long-term space travel is the risk of Radiation Exposure Induced Death (REID). The National Aeronautics and Space Administration (NASA) has adopted Permissible Exposure Levels (PELs) to limit the probability of REID to 3% for the risk of death due to radiation-induced carcinogenesis. The most significant contributor to current REID estimates for astronauts is the risk of lung cancer. Recently updated lung cancer estimates from Japan's atomic bomb survivors showed that the excess relative risk of lung cancer by age 70 is roughly four-fold higher in females compared to males. However, whether sex differences may impact the risk of lung cancer due to exposure to high charge and energy (HZE) radiation is not well studied. Thus, to evaluate the impact of sex differences on the risk of solid cancer development post-HZE radiation exposure, we irradiated male and female mice infected with Adeno-Cre with various doses of 320 kVp X-rays or 600 MeV/n Fe ions and monitored them for any radiation-induced malignancies. We observed that lung adenomas/carcinomas and esthesioneuroblastomas (ENBs) were the most common primary malignancies in X-ray and Fe ion-exposed mice, respectively. In addition, 1 Gy Fe ion exposure compared to X-rays led to a significantly higher incidence of lung adenomas/carcinomas (p=0.02) and ENBs (p<0.0001). However, we did not find a significantly higher incidence of any solid malignancies in female mice as compared to male mice, regardless of radiation quality. Furthermore, gene expression analysis of ENBs suggested a distinct gene expression pattern with similar hallmark pathways altered, such as MYC targets and MTORC1 signaling, in X-ray and Fe ion-induced ENBs. Thus, our data revealed that Fe ion exposure significantly accelerated the development of lung adenomas/carcinomas and ENBs compared to X-rays, but the rate of solid malignancies was similar between male and female mice, regardless of radiation quality.
长期太空旅行的主要阻碍是辐射暴露致死风险（REID）。美国国家航空航天局（NASA）已采用可接受暴露水平（PELs），将因辐射诱发癌症导致死亡的REID概率限制在3%。目前对宇航员REID估计的最大影响因素是肺癌风险。日本原子弹幸存者最近更新的肺癌估计显示，到70岁时，女性肺癌的超额相对风险比男性高出约四倍。然而，性别差异是否会影响因暴露于高电荷和能量（HZE）辐射而患肺癌的风险，目前尚未得到充分研究。因此，为了评估性别差异对HZE辐射暴露后实体癌发生风险的影响，我们用不同剂量的320 kVp X射线或600 MeV/n铁离子照射感染腺病毒-Cre的雄性和雌性小鼠，并监测它们是否发生任何辐射诱发的恶性肿瘤。我们观察到，在X射线和铁离子暴露的小鼠中，肺腺瘤/癌和嗅神经母细胞瘤（ENBs）分别是最常见的原发性恶性肿瘤。此外，与X射线相比，1 Gy铁离子暴露导致肺腺瘤/癌（p = 0.02）和ENBs（p < 0.0001）的发生率显著更高。然而，无论辐射质量如何，我们都未发现雌性小鼠的任何实体恶性肿瘤发生率显著高于雄性小鼠。此外，对ENBs的基因表达分析表明，在X射线和铁离子诱导的ENBs中，存在一种独特的基因表达模式，具有相似的标志性通路改变，如MYC靶点和MTORC1信号通路。因此，我们的数据表明，与X射线相比，铁离子暴露显著加速了肺腺瘤/癌和ENBs的发展，但无论辐射质量如何，雄性和雌性小鼠的实体恶性肿瘤发生率相似。
