Abstract
A sensitive biodosimetry tool is required for rapid individualized dose estimation and risk assessment in the case of radiological or nuclear mass casualty scenarios to prioritize exposed humans for immediate medical countermeasures to reduce radiation related injuries or morbidity risks. Unlike the conventional Dicentric Chromosome Assay (DCA), which takes about 3–4 days for radiation dose estimation, cell fusion mediated Premature Chromosome Condensation (PCC) technique in G0 lymphocytes can be rapidly performed for radiation dose assessment within 6–8 hrs of sample receipt by alleviating the need for ex vivo lymphocyte proliferation for 48 hrs. Despite this advantage, the PCC technique has not yet been fully exploited for radiation biodosimetry. Realizing the advantage of G0 PCC technique that can be instantaneously applied to unstimulated lymphocytes, we evaluated the utility of G0 PCC technique in detecting ionizing radiation (IR) induced stable and unstable chromosomal aberrations for biodosimetry purposes. Our study demonstrates that PCC coupled with mFISH and mBAND techniques can efficiently detect both numerical and structural chromosome aberrations at the intra- and inter-chromosomal levels in unstimulated T- and B-lymphocytes. Collectively, we demonstrate that the G0 PCC technique has the potential for development as a biodosimetry tool for detecting unstable chromosome aberrations (chromosome fragments and dicentric chromosomes) for early radiation dose estimation and stable chromosome exchange events (translocations) for retrospective monitoring of individualized health risks in unstimulated lymphocytes.
Highlights
Exposure to ionizing radiation (IR) can adversely affect human health including mortality from acute radiation syndrome with a LD50/30 value of 3.5 Gy-4.5 Gy without treatment and 6.5 Gy- 7.5 Gy with appropriate therapy
The G0 Premature Chromosome Condensation (PCC)-fluorescence in situ hybridization (FISH) technique is distinctly advantageous because the turnaround time for radiation dose assessment is dramatically reduced (6–8 hrs after the receipt of blood samples relative to 72–96 hrs by the conventional Dicentric Chromosome Assay (DCA))
The frequency of dicentric chromosomes was analyzed in the present study by centromere and telomere FISH in G0 PCCs obtained at 6 hrs after exposure to varying doses of γ-rays (0 Gy, 1 Gy, 2 Gy, 4 Gy and 6 Gy)
Summary
Exposure to ionizing radiation (IR) can adversely affect human health including mortality from acute radiation syndrome with a LD50/30 value of 3.5 Gy-4.5 Gy without treatment and 6.5 Gy- 7.5 Gy with appropriate therapy. It is imperative to determine the absorbed radiation dose to initiate appropriate medical countermeasures. Bender and Gooch (1962) reported for the first time that the detection of dicentric chromosomes (DCs) in peripheral blood lymphocytes can be reflective of the absorbed radiation dose in exposed humans. Dicentric Chromosome Assay (DCA) has been routinely used for radiation dose assessment of either occupationally or accidentally exposed humans. The conventional DCA requires the stimulation of T-lymphocytes in vitro by Phytohaemagglutinin-M (PHA-M) for at least 48 hrs with an additional time of 24–48 hrs for cell fixation, DC analysis and radiation dose estimation. Rapid individualized dose assessment is an absolute requirement for segregating people with moderate or high radiation exposure from non-exposed but “worriedwell” population so that individuals who need urgent care can be prioritized for treatment
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