title: 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.
authors.affiliation: Health Protection Agency Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire, United Kingdom. sjh.horn@gmail.com
authors.forename: Simon
authors.initials: S
authors.lastname: Horn
authors.forename: Stephen
authors.initials: S
authors.lastname: Barnard
authors.forename: Kai
authors.initials: K
authors.lastname: Rothkamm
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005434:Flow Cytometry; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D014965:X-Rays; D055815:Young Adult
chemical_list: C468783:H2AX protein, human; D006657:Histones