Toward the development of transcriptional biodosimetry for the identification of irradiated individuals and assessment of absorbed radiation dose

Abstract

The most frequently used and the best established method of biological dosimetry at present is the dicentric chromosome assay, which is poorly suitable for a mass casualties scenario. This gives rise to the need for the development of new, high-throughput assays for rapid identification of the subjects exposed to ionizing radiation. In the present study, we tested the usefulness of gene expression analysis in blood cells for biological dosimetry. Human peripheral blood from three healthy donors was X-irradiated with doses of 0 (control), 0.6, and 2 Gy. The mRNA level of 16 genes (ATF3, BAX, BBC3, BCL2, CDKN1A, DDB2, FDXR, GADD45A, GDF15, MDM2, PLK3, SERPINE1, SESN2, TNFRSF10B, TNFSF4, and VWCE) was assessed by reverse transcription quantitative PCR 6, 12, 24, and 48 h after exposure with ITFG1 and DPM1 used as a reference genes. The panel of radiation-responsive genes was selected comprising GADD45A, CDKN1A, BAX, BBC3, DDB2, TNFSF4, GDF15, and FDXR. Cluster analysis showed that ΔCt values of the selected genes contained sufficient information to allow discrimination between irradiated and non-irradiated blood samples. The samples were clearly grouped according to the absorbed doses of radiation and not to the time interval after irradiation or to the blood donor.Electronic supplementary materialThe online version of this article (doi:10.1007/s00411-015-0603-8) contains supplementary material, which is available to authorized users.

Impact of ATM and DNA-PK Inhibition on Gene Expression and Individual Response of Human Lymphocytes to Mixed Beams of Alpha Particles and X-Rays

“…Radiation-induced gene expression in PBL is regarded as a promising retrospective biological dosimeter [32,33]. Due to its high responsiveness to radiation, the FDXR gene appears as a particularly suitable biodosimeter in cases where sample collection is possible within a short time after exposure [24].…”

Gene expression-based biodosimetry for radiological incidents: assessment of dose and time after radiation exposure

“…A promising new approach for biodosimetry that offers superior time-efficiency (Abend et al 2016), is the analysis of changes in gene expression levels. Several genes, which respond to radiation exposure have been studied using different methodological approaches, such as whole genome microarray methods (Dressman et al 2007;Fachin et al 2007;Paul and Amundson 2008;Boldt et al 2012;Knops et al 2012;Macaeva et al 2016) or quantitative PCR (Joiner et al 2011;Kabacik et al 2011;Manning et al 2013;Tucker et al 2014;Brzoska and Kruszewski 2015). Most of the identified genes are known to be regulated by p53 (e.g.…”

Comparable dose estimates of blinded whole blood samples are obtained independently of culture conditions and analytical approaches. Second RENEB gene expression study

“…In ex vivo studies, several protocols have been used such as cultured peripheral blood mononuclear cells (PBMC) (Dressman et al 2007;Meadows et al 2008Meadows et al , 2010Sprung et al 2011;Boldt et al 2012;Knops et al 2012;Riecke et al 2012;Macaeva et al 2016), cultured whole blood diluted with media Brzoska andKruszewski 2015, Abend et al 2016) or undiluted whole blood (Manning et al 2013). However, none of these studies have addressed the role of blood culture methods during the incubation time at 37 C following radiation exposure.…”