GAMMA H2AX

Gamma H2AX foci formation in lymphocytes in vivo is increased one hour after very low dose X-radiation in three young children

[Name of the Writer]

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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 o-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 o-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 o-H2AX calibration function, were in good agreement with the actual mixing ratios and doses delivered to the samples. In conclusion, o-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.

Gamma H2AX foci formation in lymphocytes in vivo is increased one hour after very low dose X-radiation in three young children

Introduction

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. However, most human radiation exposures are partial body exposures, whether during planned medical exposures or in the case of radiation accidents. Information about the extent of 'sparing' of normal tissues during a high dose exposure and accurate estimates of peak doses delivered to localised regions of the body are of crucial importance for the clinical management of radiation casualties. To address this need, analytical methods have been developed for the long-established 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. In contrast, many of the emerging biological dosimetry techniques, which focus on quick dose assessments to facilitate rapid triage, have not been tested as rigorously in cases of ...