Salah Ahmed, Wollschläger Daniel, Callari Maurizio, Schmidberger Heinz, Marini Federico, Zahnreich Sebastian
Department of Radiation Oncology and Radiation Therapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Sci Rep. 2025 Jun 5;15(1):19840. doi: 10.1038/s41598-025-04898-1.
Blood cells are affected in nearly all ionizing radiation exposure scenarios. Whole transcriptome data offer detailed insights into blood's radiation response, crucial for radiotherapy and biodosimetry. We conducted genome-wide RNA-seq analysis on blood from three donors irradiated ex vivo with X-rays and incubated for 2 h and 6 h. Gene expression was subject to strong inter-donor variation and time post-exposure. After 0.5, 1, 2, and 4 Gy X-rays, 5, 33, 84, and 364 genes (2 h) and 72, 99, 274, and 607 genes (6 h) were differentially expressed (DEG), compared to 0 Gy. The corresponding number of the inferred transcription factors was 255, 253, 274, and 292 after 2 h and 214, 245, 262, and 279 after 6 h. In sham-irradiated blood, 924 DEGs and 165 transcription factors were affected by ex vivo incubation alone. We identified 34 radioresponsive DEGs not previously described, 8 and 9 showing significant positive or negative correlations with dose, respectively, including GPN1, MRM2, G0S2, and PTPRS. DNA damage signaling pathways were affected from the lowest dose, with doses ≥ 2 Gy additionally triggering proinflammatory responses. This genome-wide RNA-seq study of ex vivo X-ray-exposed human blood reveals novel radiosensitive genes, transcription factors, and pathways, enhancing the understanding of the consequences of diagnostic, therapeutic, or accidental exposures on the highly radioresponsive blood system.
几乎在所有电离辐射暴露场景中血细胞都会受到影响。全转录组数据能提供关于血液辐射反应的详细见解，这对放射治疗和生物剂量测定至关重要。我们对三名供体的血液进行了全基因组RNA测序分析，这些血液在体外接受X射线照射，并分别孵育2小时和6小时。基因表达存在强烈的供体间差异以及暴露后的时间差异。与0 Gy相比，在接受0.5、1、2和4 Gy X射线照射后，分别有5、33、84和364个基因（2小时）以及72、99、274和607个基因（6小时）差异表达（DEG）。2小时后相应的推断转录因子数量为255、253、274和292个，6小时后为214、245、262和279个。在假照射的血液中，仅体外孵育就影响了924个DEG和165个转录因子。我们鉴定出34个先前未描述的辐射反应性DEG，其中8个和9个分别与剂量呈显著正相关或负相关，包括GPN1、MRM2、G0S2和PTPRS。DNA损伤信号通路从最低剂量开始就受到影响，剂量≥2 Gy时还会引发促炎反应。这项对体外X射线照射的人血进行的全基因组RNA测序研究揭示了新的辐射敏感基因、转录因子和信号通路，增进了我们对诊断性、治疗性或意外暴露对高度辐射敏感的血液系统所产生后果的理解。
