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染色体易位、倒位与端粒长度可用于回溯性生物剂量测定美国原子老兵的暴露。

Chromosome Translocations, Inversions and Telomere Length for Retrospective Biodosimetry on Exposed U.S. Atomic Veterans.

机构信息

a Cell and Molecular Biology Program, Colorado State University, Fort Collins, Colorado.

b Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado.

出版信息

Radiat Res. 2019 Apr;191(4):311-322. doi: 10.1667/RR15240.1. Epub 2019 Feb 4.

DOI:10.1667/RR15240.1
PMID:30714852
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6492561/
Abstract

It has now been over 60 years since U.S. nuclear testing was conducted in the Pacific islands and Nevada, exposing military personnel to varying levels of ionizing radiation. Actual doses are not well-established, as film badges in the 1950s had many limitations. We sought a means of independently assessing dose for comparison with historical film badge records and dose reconstruction conducted in parallel. For the purpose of quantitative retrospective biodosimetry, peripheral blood samples from 12 exposed veterans and 12 age-matched (>80 years) veteran controls were collected and evaluated for radiation-induced chromosome damage utilizing directional genomic hybridization (dGH), a cytogenomics-based methodology that facilitates simultaneous detection of translocations and inversions. Standard calibration curves were constructed from six male volunteers in their mid-20s to reflect the age range of the veterans at time of exposure. Doses were estimated for each veteran using translocation and inversion rates independently; however, combining them by a weighted-average generally improved the accuracy of dose estimations. Various confounding factors were also evaluated for potential effects on chromosome aberration frequencies. Perhaps not surprisingly, smoking and age-associated increases in background frequencies of inversions were observed. Telomere length was also measured, and inverse relationships with both age and combined weighted dose estimates were observed. Interestingly, smokers in the non-exposed control veteran cohort displayed similar telomere lengths as those in the never-smoker exposed veteran group, suggesting that chronic smoking had as much effect on telomere length as a single exposure to radioactive fallout. Taken together, we find that our approach of combined chromosome aberration-based retrospective biodosimetry provided reliable dose estimation capability, particularly on a group average basis, for exposures above statistical detection limits.

摘要

自美国在太平洋岛屿和内华达州进行核试验以来,已经过去了 60 多年,这使得军事人员暴露在不同程度的电离辐射下。由于 20 世纪 50 年代的胶片徽章存在许多局限性,实际剂量尚未得到很好的确定。我们寻求一种独立评估剂量的方法,以便与历史胶片徽章记录和并行进行的剂量重建进行比较。为了进行定量回顾性生物剂量测定,我们收集了 12 名暴露老兵和 12 名年龄匹配(>80 岁)老兵对照者的外周血样本,并利用定向基因组杂交(dGH)评估辐射引起的染色体损伤,dGH 是一种基于细胞遗传学的方法,可促进易位和倒位的同时检测。从六名 20 多岁的男性志愿者中构建了标准校准曲线,以反映暴露时老兵的年龄范围。使用易位和倒位率独立地为每位老兵估计剂量;但是,通过加权平均值将它们组合通常可以提高剂量估计的准确性。还评估了各种混杂因素对染色体畸变频率的潜在影响。也许并不奇怪,观察到吸烟和与年龄相关的倒位背景频率增加。还测量了端粒长度,并观察到与年龄和加权剂量估计值的逆相关关系。有趣的是,未暴露对照老兵队列中的吸烟者显示出与从不吸烟者暴露老兵组相似的端粒长度,这表明慢性吸烟对端粒长度的影响与单次放射性沉降物暴露一样大。总的来说,我们发现我们的基于染色体畸变的回顾性生物剂量测定方法提供了可靠的剂量估计能力,特别是在群体平均水平上,对于高于统计检测限的暴露。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff8c/6492561/e218aafc3784/nihms-1023940-f0008.jpg
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