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应用 calyculin A 诱导的早熟染色体凝聚物评分系统进行剂量评估,包括对放疗患者的评估。

Applicability of Scoring Calyculin A-Induced Premature Chromosome Condensation Objects for Dose Assessment Including for Radiotherapy Patients.

机构信息

UK Health Security Agency (UKHSA), Department of Radiation Effects, Cytogenetics and Pathology Group, RCEHD, Didcot, UK.

Division of Radiotherapy and Imaging, The Institute of Cancer Research (ICR), Sutton, UK.

出版信息

Cytogenet Genome Res. 2023;163(3-4):143-153. doi: 10.1159/000534656. Epub 2023 Oct 25.

Abstract

As an extension to a previous study, a linear calibration curve covering doses from 0 to 10 Gy was constructed and evaluated in the present study using calyculin A-induced premature chromosome condensation (PCC) by scoring excess PCC objects. The main aim of this study was to assess the applicability of this PCC assay for doses below 2 Gy that are critical for triage categorization. Two separate blind tests involving a total of 6 doses were carried out; 4 out of 6 dose estimates were within the 95% confidence limits (95% CL) with the other 2 just outside. In addition, blood samples from five cancer patients undergoing external beam radiotherapy (RT) were also analyzed, and the results showed whole-body dose estimates statistically comparable to the dicentric chromosome assay (DCA) results. This is the first time that calyculin A-induced PCC was used to analyze clinical samples by scoring excess objects. Although dose estimates for the pre-RT patient samples were found to be significantly higher than the mean value for the healthy donors and were also significantly higher than those obtained using DCA, all these pre-treatment patients fell into the same category as those who may have received a low dose (<1 Gy) and do not require immediate medical care during emergency triage. Additionally, for radiological accidents with unknown exposure scenario, PCC objects and rings can be scored in parallel for the assessment of both low- and high-dose exposures. In conclusion, scoring excess objects using calyculin A-induced PCC is confirmed to be another potential biodosimetry tool in radiological emergency particularly in mass casualty scenarios, even though the data need to be interpreted with caution when cancer patients are among the casualties.

摘要

作为之前一项研究的延伸,本研究使用细胞松弛素 A 诱导的早熟染色体凝聚 (PCC) 通过计数过多的 PCC 物体来构建和评估涵盖 0 至 10 Gy 剂量的线性校准曲线。本研究的主要目的是评估这种 PCC 测定法在 2 Gy 以下剂量下的适用性,这对于分类至关重要。进行了两项单独的盲测,总共涉及 6 个剂量;6 个剂量估计中有 4 个在 95%置信限(95%CL)内,另外 2 个刚好在置信限外。此外,还分析了五名接受外束放射治疗(RT)的癌症患者的血液样本,结果表明全身剂量估计与双着丝粒染色体测定法(DCA)结果具有统计学可比性。这是首次使用细胞松弛素 A 诱导的 PCC 通过计数过多的物体来分析临床样本。尽管发现预 RT 患者样本的剂量估计值明显高于健康供体的平均值,并且也明显高于 DCA 获得的值,但所有这些预处理患者都归入与那些可能接受低剂量(<1 Gy)且在紧急分类中不需要立即医疗的患者相同的类别。此外,对于暴露情况未知的放射性事故,可以并行评分 PCC 物体和环,以评估低剂量和高剂量暴露。总之,使用细胞松弛素 A 诱导的 PCC 计数过多的物体被证实是放射紧急情况下(尤其是在大规模伤亡情况下)的另一种潜在的生物剂量测定工具,尽管在有癌症患者伤亡的情况下,数据需要谨慎解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6978/10946622/c3f794e8a734/cgr-2023-0163-03-4-534656_F01.jpg

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