Abstract
Purpose: For triage purposes following a nuclear accident or a terrorist event, gene expression biomarkers in blood have been demonstrated to be good bioindicators of ionizing radiation (IR) exposure and can be used to assess the dose received by exposed individuals. Many IR-sensitive genes are regulated by the DNA damage response pathway, and modulators of this pathway could potentially affect their expression level and therefore alter accurate dose estimations. In the present study, we addressed the potential influence of temperature, sample transport conditions and the blood cell fraction analyzed on the transcriptional response of the following radiation-responsive genes: FDXR, CCNG1, MDM2, PHPT1, APOBEC3H, DDB2, SESN1, P21, PUMA, and GADD45.
Materials and Methods: Whole blood from healthy donors was exposed to a 2 Gy X-ray dose with a dose rate of 0.5 Gy/min (output 13 mA, 250 kV peak, 0.2 mA) and incubated for 24 h at either 37, 22, or 4 °C. For mimicking the effect of transport conditions at different temperatures, samples incubated at 37 °C for 24 h were kept at 37, 22 or 4 °C for another 24 h. Comparisons of biomarker responses to IR between white blood cells (WBCs), peripheral blood mononuclear cells (PBMCs) and whole blood were carried out after a 2 Gy X-ray exposure and incubation at 37 °C for 24 hours.
Results: Hypothermic conditions (22 or 4 °C) following irradiation drastically inhibited transcriptional responses to IR exposure. However, sample shipment at different temperatures did not affect gene expression level except for SESN1. The transcriptional response to IR of specific genes depended on the cell fraction used, apart from FDXR, CCNG1, and SESN1.
Conclusion: In conclusion, temperature during the incubation period and cell fraction but not the storing conditions during transport can influence the transcriptional response of specific genes. However, FDXR and CCNG1 showed a consistent response under all the different conditions tested demonstrating their reliability as individual biological dosimetry biomarkers.
| Original language | English |
|---|---|
| Pages (from-to) | 675-686 |
| Number of pages | 12 |
| Journal | International Journal of Radiation Biology |
| Volume | 97 |
| Issue number | 5 |
| Early online date | 7 Apr 2021 |
| DOIs | |
| Publication status | Published - 4 May 2021 |
Bibliographical note
Funding Information: This study is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Chemical and Radiation Threats and Hazards, a partnership between Public Health England and Imperial College London. The views expressed are those of the author(s) and not necessarily those of the NIHR, Public Health England or the Department of Health and Social Care.Open Access: This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
Publisher Copyright: © 2021 The Author(s). Published with license by Taylor and Francis Group, LLC.
Citation: Farah Nasser, Lourdes Cruz-Garcia, Grainne O’Brien & Christophe Badie (2021) Role of blood derived cell fractions, temperature and sample transport on gene expression-based biological dosimetry, International Journal of Radiation Biology, 97:5, 675-686,
DOI: 10.1080/09553002.2021.1906464
Keywords
- FDXR
- blood derived cells
- gene expression
- temperature
- transport conditions
