Gamma-H2AX-Based Dose Estimation for Whole and Partial Body Radiation Exposure

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.

DNA Damage in Peripheral Blood Lymphocytes of Thyroid Cancer Patients After Radioiodine Therapy

“…The range of our RIF/cell decay rate for the fast component is within the value ranges of Horn et al (24) and Mariotti et al (25) (0.23 h 21 ). The slow decay component by Mariotti et al does not contribute greatly to the decay of RIF/cell (probability, 9%) and is less than 10 211 h 21 .…”

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“…A two component exponential model was used to fit the γH2AX repair kinetics data (see Figure 3), adapted from Horn et al (Horn et al 2011). To calculate the half life of the fast (T 1/2 Fast) and slow (T 1/2 Slow) component, each component was multiplied by the natural logarithm of 2:…”

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“…Therefore, this method is suited more for planned exposures such as diagnostic radiology [32] or radiotherapy [33]. As a biodosimetry technique, it is useful immediately after exposure, as foci levels peak at ,1 h but then decline within days [34]. Developments have been made to increase speed and throughput of results by measuring g-H2AX intensity instead of scoring the number of foci [35], but this, as with most automated techniques, results in lower sensitivity.…”