Center for Radiological Research, Columbia University, New York, New York, USA.
Currently at: Loma Linda University Medical Center, Loma Linda, California, USA.
Cytogenet Genome Res. 2023;163(3-4):110-120. doi: 10.1159/000533488. Epub 2023 Aug 12.
Following a mass-casualty nuclear/radiological event, there will be an important need for rapid and accurate estimation of absorbed dose for biological triage. The cytokinesis-block micronucleus (CBMN) assay is an established and validated cytogenetic biomarker used to assess DNA damage in irradiated peripheral blood lymphocytes. Here, we describe an intercomparison experiment between two biodosimetry laboratories, located at Columbia University (CU) and Health Canada (HC) that performed different variants of the human blood CBMN assay to reconstruct dose in human blood, with CU performing the assay on isolated lymphocytes and using semi-automated scoring whereas HC used the more conventional whole blood assay. Although the micronucleus yields varied significantly between the two assays, the predicted doses closely matched up to 4 Gy - the range from which the HC calibration curve was previously established. These results highlight the importance of a robust calibration curve(s) across a wide age range of donors that match the exposure scenario as closely as possible and that will account for differences in methodology between laboratories. We have seen that at low doses, variability in the results may be attributed to variation in the processing while at higher doses the variation is dominated by inter-individual variation in cell proliferation. This interlaboratory collaboration further highlights the usefulness of the CBMN endpoint to accurately reconstruct absorbed dose in human blood after ionizing radiation exposure.
在大规模人员伤亡的核/放射性事件发生后,人们将迫切需要快速、准确地估算生物分拣的吸收剂量。有丝分裂阻滞微核(CBMN)试验是一种已建立和验证的细胞遗传学生物标志物,用于评估辐照外周血淋巴细胞中的 DNA 损伤。在这里,我们描述了位于哥伦比亚大学(CU)和加拿大卫生部(HC)的两个生物剂量学实验室之间的一项对比实验,这两个实验室使用不同的人血 CBMN 试验变体来重建人血中的剂量,CU 在分离的淋巴细胞上进行试验,并使用半自动评分,而 HC 使用更传统的全血试验。尽管两种试验的微核产量差异很大,但预测剂量在 4Gy 以内非常吻合,这是 HC 校准曲线之前建立的范围。这些结果强调了在尽可能接近暴露情况的情况下,针对广泛的供体年龄范围建立稳健的校准曲线的重要性,并且要考虑到实验室之间方法学的差异。我们已经看到,在低剂量下,结果的可变性可能归因于处理过程中的差异,而在高剂量下,变异主要由细胞增殖的个体间差异主导。这种实验室间的合作进一步突出了 CBMN 终点在准确重建人类血液中吸收剂量方面的有用性。