Establishment and validation of surface model for biodosimetry based on γ-H2AX foci detection

Abstract

Introduction

In the event of a radiation accident detecting γ-H2AX foci is being accepted as fast method for triage and dose assessment. However, due to their disappearance kinetics, published calibrations have been constructed at specific post-irradiation times.

Objectives

To develop a surface, or tridimensional, model to estimate doses at times not included in the calibration analysis, and to validate it.

Materials and methods

Calibration data was obtained irradiating peripheral mononucleated cells from one donor with radiation doses ranging from 0 to 3 Gy, and γ -H2AX foci were detected microscopically using a semi-automatic method, at different post-irradiation times from 0.5 to 24 h. For validation, in addition to the above-mentioned donor, blood samples from another donor were also used. Validation was done within the range of doses and post-irradiation times used in the calibration.

Results

The calibration data clearly shows that at each analyzed time, the γ-H2AX foci frequency increases as dose increases, and for each dose this frequency decreases with post-irradiation time. The γ-H2AX foci nucleus distribution was clearly overdispersed, for this reason to obtain bidimensional and tridimensional dose-effect relationships no probability distribution was assumed, and linear and non-linear least squares weighted regression was used. In the two validation exercises for most evaluated samples, the 95% confidence limits of the estimated dose were between ±0.5 Gy of the real dose. No major differences were observed between donors.

Conclusion

In case of a suspected overexposure to radiation, the surface model here presented allows a correct dose estimation using γ-H2AX foci as biomarker. The advantage of this surface model is that it can be used at any post-irradiation time, in our model between 0.5 and 24 h.

Keywords:

• γ-H2AX
• biodosimetry
• surface model
• ionizing radiation

Acknowledgements

MR, PC, GA and JFB are part of a SGR recognized by the Generalitat de Catalunya (2017SGR0255).

Disclosure statement

No conflict of interest was reported by the authors.

Additional information

Notes on contributors

Juan S. López

Juan S. López, Histocytologist, PhD student, Department of Animal Biology, Plant Biology and Ecology, Faculty of Biosciencies, Universitat Autònoma de Barcelona (UAB), Bellaterra (Cerdanyola del Vallès), Catalonia, Spain.

Mònica Pujol-Canadell

Mònica Pujol-Canadell, PhD, Biologist, Postdoctoral research scientist at the Department of Animal Biology, Plant Biology and Ecology, Faculty of Biosciències, Universitat Autònoma de Barcelona (UAB), Bellaterra (Cerdanyola del Vallès), Catalonia, Spain.

Pedro Puig

Pedro Puig, PhD, Mathematician, Professor at the Department of Mathematics and member of the Center de Recerca Matemàtica, Faculty of Sciences, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallés), Catalonia, Spain.

Montserrat Ribas

Montserrat Ribas, PhD. in Physics, Medical Physicist, ex-Head of the Department of Radiation Physics and Radiation Protection at the Hospital Santa Creu i Sant Pau, Barcelona, Spain.

Pablo Carrasco

Pablo Carrasco, PhD, Physicist, Radiation Physics and Radiation Protection Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Gemma Armengol

Gemma Armengol, PhD, Biologist, University Professor at the Department of Animal Biology, Plant Biology and Ecology, Faculty of Biosciencies, Universitat Autònoma de Barcelona (UAB), Bellaterra (Cerdanyola del Vallès), Spain.

Joan F. Barquinero

Joan-Francesc Barquinero, PhD, Biologist, University Professor at the Department of Animal Biology, Plant Biology and Ecology, Faculty of Biosciencies, Universitat Autònoma de Barcelona (UAB), Bellaterra (Cerdanyola del Vallès), Spain.