Pseudo Pelger-Huët anomalies as potential biomarkers for acute exposure radiation dose in rhesus macaques (Macaca mulatta).
Pseudo Pelger-Huët anomalies as potential biomarkers for acute exposure radiation dose in rhesus macaques (Macaca mulatta).
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DOI：
10.1080/09553002.2021.1998708
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发表时间：
2022
影响因子：
2.6
通讯作者：
中科院分区：
文献类型：
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作者：
恶意使用辐射或辐射事故的可能性可能会对公众造成严重的高辐射剂量。在急性意外暴露于高剂量辐射后，医疗干预对患者的生存能力至关重要，越早采取适当措施，生存的可能性就越大。急性事故辐射剂量的早期估计可通过生物标志物确定，如双着丝粒染色体分析或使用计算机软件进行情景重建。然而，这两种方法都需要宝贵的时间，而且可能很昂贵。外周血中异常中性粒细胞的频率增加，称为假Pelger-Huët异常（PPHA），已被证明是几种情况下辐射暴露的潜在生物标志物，包括1958年Y-12临界事故和镭表盘油漆工。PPHA可能是辐射暴露的更快，更便宜的定量生物标志物，在这里，他们在急性暴露的恒河猴进行了评估。使用光学显微镜评价急性暴露恒河猴外周血涂片中显示PPHA形态的中性粒细胞百分比。采用以下两种策略之一，辐照动物接受0至8.5戈伊的全身辐射：（1）线性加速器产生的6 MV光子，以80 c戈伊/min的速度递送;或（2）钴60产生的γ辐射以60 cGy/min的速度传递。零剂量动物用于确定PPHA的基线百分比，在辐照后受照动物的整个生命周期内定期采集血液涂片，用于确定PPHA的持久性和生物活性。恒河猴中PPHA的基线患病率确定为0.58 ± 0.46%。剂量范围为0戈伊至8.5戈伊（LD 90/30）的剂量反应曲线显示，PPHA百分比与急性辐射剂量之间存在强正相关性（R2为0.88 p = 3.62 × 10−22）。当将动物分为0、4、6.4-6.5和8-8.5戈伊剂量队列时，发现了统计学显著差异。生物学模型仅使用4戈伊照射，并在照射后3.1年内定期采集血液涂片。PPHA形态在照射后迅速增加，并且在照射后3.1年内稳定。证实了恒河猴体内存在PPHA形态，并建立了剂量-反应关系，且在照射后3年内保持稳定。本研究表明，PPHA分析可以是一种快速，廉价的生物剂量学方法。未来的研究将致力于确定剂量测定的准确性和检测下限。
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 (R2 of 0.88 p = 3.62 × 10−22). 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.
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影响因子：
2.2
作者：
Sullivan JM;Prasanna PG;Grace MB;Wathen LK;Wallace RL;Koerner JF;Coleman CN
通讯作者：
Coleman CN
影响因子：
2.2
作者：
Farese AM;Cohen MV;Katz BP;Smith CP;Jackson W 3rd;Cohen DM;MacVittie TJ
通讯作者：
MacVittie TJ
DOI：
10.1016/0027-5107(95)00049-o
发表时间：
1995-09-01
影响因子：
2.3
作者：
RAMALHO, AT;CURADO, MP;NATARAJAN, AT
通讯作者：
NATARAJAN, AT
影响因子：
3.7
作者：
Yu, Wenhai;Hao, Xianhui;He, Zhanlong
通讯作者：
He, Zhanlong
DOI：
10.4049/jimmunol.181.8.5183
发表时间：
2008-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
von Vietinghoff S;Ley K
通讯作者：
Ley K