PDF(Pubmed)
Abstract：
High dose radiation exposures are rare. However, medical management of such incidents is crucial due to mortality and tissue injury risks. Rapid radiation biodosimetry of high dose accidental exposures is highly challenging, considering that they usually involve non uniform fields leading to partial body exposures. The gold standard, dicentric assay and other conventional methods have limited application in such scenarios. As an alternative, we propose Premature Chromosome Condensation combined with Fluorescent In-situ Hybridization (G0-PCC-FISH) as a promising tool for partial body exposure biodosimetry. In the present study, partial body exposures were simulated ex-vivo by mixing of uniformly exposed blood with unexposed blood in varying proportions. After G0-PCC-FISH, Dolphin\'s approach with background correction was used to provide partial body exposure dose estimates and these were compared with those obtained from conventional dicentric assay and G0-PCC-Fragment assay (conventional G0-PCC). Dispersion analysis of aberrations from partial body exposures was carried out and compared with that of whole-body exposures. The latter was inferred from a multi-donor, wide dose range calibration curve, a-priori established for whole-body exposures. With the dispersion analysis, novel multi-parametric methodology for discerning the partial body exposure from whole body exposure and accurate dose estimation has been formulated and elucidated with the help of an example. Dose and proportion dependent reduction in sensitivity and dose estimation accuracy was observed for Dicentric assay, but not in the two PCC methods. G0-PCC-FISH was found to be most accurate for the dose estimation. G0-PCC-FISH has potential to overcome the shortcomings of current available methods and can provide rapid, accurate dose estimation of partial body and high dose accidental exposures. Biological dose estimation can be useful to predict progression of disease manifestation and can help in pre-planning of appropriate & timely medical intervention.
摘要：
高剂量辐射照射是罕见的。然而,由于死亡率和组织损伤风险，对此类事件的医疗管理至关重要。高剂量意外暴露的快速辐射生物剂量学非常具有挑战性，考虑到它们通常涉及导致部分身体曝光的非均匀场。黄金标准,双中心测定和其他常规方法在这种情况下的应用有限。作为替代,我们建议将染色体早缩结合荧光原位杂交（G0-PCC-FISH）作为部分身体暴露生物剂量测定的有前途的工具。在本研究中,通过将均匀暴露的血液与未暴露的血液以不同比例混合来模拟体外部分身体暴露。在G0-PCC-FISH之后，使用带有背景校正的海豚方法来提供部分身体暴露剂量估计，并将其与从常规双中心测定和G0-PCC-片段测定（常规G0-PCC）获得的剂量进行比较。对部分身体暴露的像差进行了色散分析，并与全身暴露的像差进行了比较。后者是从多捐赠者推断出来的，宽剂量范围校准曲线，为全身暴露而建立的先验。通过色散分析，在示例的帮助下，已经制定并阐明了用于从全身暴露中辨别部分身体暴露和准确剂量估计的新颖多参数方法。Dicentric测定法观察到灵敏度和剂量估计准确性的剂量和比例依赖性降低，但不是在两种PCC方法中。发现G0-PCC-FISH对于剂量估计最准确。G0-PCC-FISH有可能克服当前可用方法的缺点，并且可以提供快速，部分身体和高剂量意外暴露的准确剂量估计。生物剂量估计可用于预测疾病表现的进展,并且可帮助预先规划适当和及时的医疗干预。
