Abstract
Most human exposures to ionising radiation are partial body exposures. However, to date only limited tools are available for rapid and accurate estimation of the dose distribution and the extent of the body spared from the exposure. These parameters are of great importance for emergency triage and clinical management of exposed individuals. Here, measurements of γ-H2AX immunofluorescence by microscopy and flow cytometry were compared as rapid biodosimetric tools for whole and partial body exposures. Ex vivo uniformly X-irradiated blood lymphocytes from one donor were used to generate a universal biexponential calibration function for γ-H2AX foci/intensity yields per unit dose for time points up to 96 hours post exposure. Foci – but not intensity – levels remained significantly above background for 96 hours for doses of 0.5 Gy or more. Foci-based dose estimates for ex vivo X-irradiated blood samples from 13 volunteers were in excellent agreement with the actual dose delivered to the targeted samples. Flow cytometric dose estimates for X-irradiated blood samples from 8 volunteers were in excellent agreement with the actual dose delivered at 1 hour post exposure but less so at 24 hours post exposure. In partial body exposures, simulated by mixing ex vivo irradiated and unirradiated lymphocytes, foci/intensity distributions were significantly over-dispersed compared to uniformly irradiated lymphocytes. For both methods and in all cases the estimated fraction of irradiated lymphocytes and dose to that fraction, calculated using the zero contaminated Poisson test and γ-H2AX calibration function, were in good agreement with the actual mixing ratios and doses delivered to the samples. In conclusion, γ-H2AX analysis of irradiated lymphocytes enables rapid and accurate assessment of whole body doses while dispersion analysis of foci or intensity distributions helps determine partial body doses and the irradiated fraction size in cases of partial body exposures.
Highlights
Dose assessments based on well established cytogenetic assays and especially those utilising emerging techniques in the field of biological dosimetry are mainly suited for whole body exposures to ionising radiation [1]
Analytical methods have been developed for the longestablished dicentric assay, the current ‘gold standard’ in biological dosimetry, to identify partial body exposures and calculate the irradiated fraction of the body and estimate peak doses to the irradiated fraction [3]
Results c-H2AX and 53BP1 foci induction is linear and loss follows a bi-exponential decay that can be approximated with one universal calibration function
Summary
Dose assessments based on well established cytogenetic assays and especially those utilising emerging techniques in the field of biological dosimetry are mainly suited for whole body exposures to ionising radiation [1]. C-H2AX and 53BP1 foci form at the sites of DSBs and can be visualised within minutes of exposure [8] Their potential for accurately estimating radiation dose has already been reported following experimental human ex vivo [9,10,11], non-human primate in vivo [12] and diagnostic [8] or therapeutic [13] human in vivo exposure. These studies demonstrate excellent sensitivity down to a few milligray, the ability of the c-H2AX assay to identify a recent partial body exposure, and persistence of foci for several days after high dose exposure
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