Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado, USA.
Biological Dosimetry Model Laboratory, Section of Applied Radiation Biology and Radiotherapy, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
Int J Radiat Biol. 2022;98(5):913-923. doi: 10.1080/09553002.2021.1998708. Epub 2021 Nov 11.
The potential for malicious use of radiation, or radiation accidents could potentially lead to acute, high radiation doses to the public. Following acute accidental exposure to high doses of radiation, medical intervention is pivotal to the survivability of the patient, and the sooner the appropriate measures are taken the better the odds for survival. Early estimates of acute accidental radiation doses can be determined via biomarkers such as dicentric chromosome analysis or scenario reconstruction using computer software. However, both take valuable time and can be expensive. Increased frequencies of abnormal neutrophils in peripheral blood, referred to as pseudo Pelger-Huët anomalies (PPHAs), have been shown to be potential biomarkers of radiation exposure in several scenarios, including the 1958 Y-12 criticality accident and the radium dial painters. PPHAs are potentially a faster and cheaper quantitative biomarker for radiation exposure, and here they were evaluated in acutely exposed rhesus macaques.
Peripheral blood smears from acutely exposed rhesus macaques were evaluated for the percentage of neutrophils that displayed the PPHA morphology using light microscopy. Irradiated animals received 0 to 8.5 Gy total body radiation using one of two strategies: (1) linear accelerator-produced 6 MV photons delivered at 80 cGy/minute; or (2) Cobalt 60-produced gamma irradiation delivered at 60 cGy/min. Zero dose animals were used to determine a baseline percentage of PPHAs, and blood smears taken periodically throughout the lifetime of exposed animals post-irradiation were used to determine the persistence and biokinetics of PPHAs.
The baseline prevalence of the PPHA in rhesus macaques was determined to be 0.58 ± 0.46%. The dose-response curve with doses ranging from 0 Gy to 8.5 Gy (LD90/30) displayed a strong positive correlation between PPHA percentage and acute radiation dose ( of 0.88 = 3.62 × 10). Statistically significant differences were found when animals were separated into dose cohorts of 0, 4, 6.4-6.5, and 8-8.5 Gy. The biokinetics model utilized only 4 Gy exposures and blood smears taken periodically over 3.1 years post-irradiation. PPHA morphology increases quickly following irradiation and appears stable over 3.1 years post-irradiation.
PPHA morphology was confirmed to be present in rhesus macaques, a dose-response relationship was constructed, and it is stable over 3 years post-irradiation. This study demonstrates that PPHA analysis can be a fast and cheap method of biodosimetry. Future studies will work to determine the accuracy of dose determination and lower limits of detection.
放射性的恶意使用或辐射事故有可能导致公众受到急性、高剂量的辐射。在急性意外暴露于高剂量辐射后，医疗干预对患者的存活率至关重要，采取适当措施的时间越早，存活的机会就越大。可以通过生物标志物（如双着丝粒染色体分析）或使用计算机软件进行情景重建来早期估计急性意外辐射剂量。然而，这两种方法都需要宝贵的时间并且可能很昂贵。外周血中异常中性粒细胞的频率增加，称为假 Pelger-Huët 异常（PPHAs），已在包括 1958 年 Y-12 临界事故和镭拨号画家在内的几种情况下被证明是辐射暴露的潜在生物标志物。PPHAs 可能是一种更快、更便宜的辐射暴露定量生物标志物，在这里对急性暴露的恒河猴进行了评估。
使用光学显微镜评估急性暴露的恒河猴外周血涂片中性粒细胞显示 PPHA 形态的百分比。受照射的动物接受了两种策略之一的全身 0 至 8.5Gy 的辐射：（1）线性加速器产生的 6MV 光子，以 80cGy/min 的速度传递；或（2）钴 60 产生的伽马辐照，以 60cGy/min 的速度传递。零剂量动物用于确定 PPHA 的基线百分比，并且在照射后动物的整个生命过程中定期采集血涂片，以确定 PPHA 的持久性和生物动力学。
确定了恒河猴中 PPHA 的基线患病率为 0.58±0.46%。剂量范围为 0Gy 至 8.5Gy（LD90/30）的剂量反应曲线显示 PPHA 百分比与急性辐射剂量之间存在很强的正相关（=0.88=3.62×10）。当将动物分为 0、4、6.4-6.5 和 8-8.5Gy 剂量组时，发现了统计学上的显著差异。生物动力学模型仅使用 4Gy 照射和照射后 3.1 年内定期采集血涂片。PPHA 形态在照射后迅速增加，并且在照射后 3.1 年内保持稳定。
证实 PPHA 形态存在于恒河猴中，构建了剂量反应关系，并在照射后 3 年保持稳定。这项研究表明，PPHA 分析可以成为一种快速且廉价的生物剂量测定方法。未来的研究将致力于确定剂量确定的准确性和更低的检测限。
