Sproull Mary, Kramp Tamalee, Tandle Anita, Shankavaram Uma, Camphausen Kevin
Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland.
Radiat Res. 2015 Jul;184(1):14-23. doi: 10.1667/RR13927.1. Epub 2015 Jun 26.
There is a need for minimally invasive biomarkers that can accurately and quickly quantify radiation exposure. Radiation-responsive proteins have applications in clinical medicine and for mass population screenings after a nuclear or radiological incident where the level of radiation exposure and exposure pattern complicate medical triage for first responders. In this study, we evaluated the efficacy of the acute phase protein serum amyloid A (SAA) as a biomarker for radiation exposure using plasma from irradiated mice. Ten-week-old female C57BL6 mice received a 1-8 Gy single whole-body or partial-body dose from a Pantak X-ray source at a dose rate of 2.28 Gy/min. Plasma was collected by mandibular or cardiac puncture at 6, 24, 48 and 72 h or 1-3 weeks postirradiation. SAA levels were determined using a commercially available ELISA assay. Data was pooled to generate SAA μg/ml threshold values correlating plasma SAA levels with radiation dose. SAA levels were statistically significant over control at all exposures between 2 and 8 Gy at 24 h postirradiation but not at 6, 48 and 72 h or 1-3 weeks postirradiation. SAA levels at 1 Gy were not significantly elevated over control at all time points. Total-body-irradiated (TBI) SAA levels at 24 h were used to generate a dose prediction model that successfully differentiated TBI mice into dose received cohorts of control/1 Gy and ≥ 2 Gy groups with a high degree of accuracy in a blind study. Dose prediction of partial-body exposures based on the TBI model correlated increasing predictive accuracy with percentage of body exposure to radiation. Our findings indicate that plasma SAA levels might be a useful biomarker for radiation exposure in a variety of total- and partial-body irradiation settings.
需要能够准确快速地量化辐射暴露的微创生物标志物。辐射反应蛋白可应用于临床医学以及核或放射性事件后的大规模人群筛查,在这类事件中,辐射暴露水平和暴露模式使急救人员的医疗分类变得复杂。在本研究中,我们使用受辐照小鼠的血浆评估了急性期蛋白血清淀粉样蛋白A(SAA)作为辐射暴露生物标志物的功效。10周龄雌性C57BL6小鼠接受来自Pantak X射线源的1 - 8 Gy单次全身或局部剂量照射,剂量率为2.28 Gy/分钟。在辐照后6、24、48和72小时或1 - 3周通过下颌或心脏穿刺采集血浆。使用市售ELISA测定法测定SAA水平。汇总数据以生成将血浆SAA水平与辐射剂量相关联的SAA μg/ml阈值。在辐照后24小时,所有2至8 Gy暴露下的SAA水平与对照组相比具有统计学意义,但在辐照后6、48和72小时或1 - 3周时无统计学意义。在所有时间点,1 Gy时的SAA水平与对照组相比均未显著升高。使用辐照后24小时的全身照射(TBI)SAA水平生成剂量预测模型,该模型在一项盲法研究中成功地将TBI小鼠高度准确地分为接受对照/1 Gy和≥2 Gy组的剂量队列。基于TBI模型的局部照射剂量预测表明,预测准确性随着身体受辐射百分比的增加而提高。我们的研究结果表明,在各种全身和局部照射情况下,血浆SAA水平可能是辐射暴露的有用生物标志物。