Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Oxfordshire, United Kingdom.
Bundeswehr Institute of Radiobiology, Munich, Germany.
Sci Rep. 2018 Jan 12;8(1):684. doi: 10.1038/s41598-017-19043-w.
Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnostic computed tomography (CT)) and treatments (total body and local radiotherapy). Moreover, a method was developed to assess the dose to the blood using physical exposure parameters. FDXR expression was significantly up-regulated 24 hr after radiotherapy in most patients and continuously during the fractionated treatment. Significance was reached even after diagnostic CT 2 hours post-exposure. We further showed that no significant differences in expression were found between ex vivo and in vivo samples from the same patients. Moreover, potential confounding factors such as gender, infection status and anti-oxidants only affect moderately FDXR transcription. Finally, we provided a first in vivo dose-response showing dose-dependency even for very low doses or partial body exposure showing good correlation between physically and biologically assessed doses. In conclusion, we report the remarkable responsiveness of FDXR to ionising radiation at the transcriptional level which, when measured in the right time window, provides accurate in vivo dose estimates.
先前关于辐射暴露后血液中基因表达变化的研究强调了其作为暴露生物标志物的潜力。在这里,研究了人类在接受一系列外部辐射暴露程序(心脏透视、诊断计算机断层扫描(CT))和治疗(全身和局部放射治疗)时血液中 FDXR 转录变化。此外,还开发了一种使用物理暴露参数评估血液剂量的方法。在大多数患者中,放射治疗后 24 小时 FDXR 表达显著上调,并在分次治疗期间持续上调。即使在暴露后 2 小时进行诊断 CT 后也达到了显著水平。我们进一步表明,来自同一患者的离体和体内样本之间的表达无明显差异。此外,性别、感染状态和抗氧化剂等潜在混杂因素仅适度影响 FDXR 转录。最后,我们提供了第一个体内剂量反应,即使对于非常低的剂量或全身部分暴露也显示出剂量依赖性,并且物理和生物评估剂量之间具有良好的相关性。总之,我们报告了 FDXR 在转录水平对电离辐射的显著反应性,当在正确的时间窗口测量时,它提供了准确的体内剂量估计。