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Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to variable CT photon spectra

ABSTRACT: In this study, we display traceable impact of energetically-varying CT irradiation on gene regulation with common upregulation of five radiation-responsive genes after single-energy (80 kV or 150kV) and dual-energy CT (80kV + 150kV) exposure. Furthermore, no evdidence for an elevated radiobiological effectiveness in respect to transcriptional impact of low energy photons emitted during dual-energy CT was found.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156187 | GEO | 2021/06/01

REPOSITORIES: GEO

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Project description:In the current global scenario there is always a possibility that a terrorist group might acquire material to produce a nuclear device. In the likelihood of a detonation of an improvised nuclear device (IND) the prompt radiation would consist of both photons (gamma rays) and neutrons. As neutrons generally have a high Relative Biological Effectiveness (RBE) for most physiological endpoints, it is important to understand the impact that neutrons would have on the biodosimetry methods that are being developed for medical triage purposes. We have previously reported transcriptomic response in human and mouse blood to neutron exposure and determined its RBE compared to photons for gene induction. In this report, we studied the effect of mixed neutron-photon radiation on gene expression in human peripheral blood in order to mimic an IND type radiation observed increase in number as well as expression level of genes with increasing percentage of neutron in mixed exposures which peaked at 25% neutron exposure which was maximum neutron percentage used for the study. We identified 156 genes that responded significantly to all the neutron-photon mixed exposures. These genes were found to be mainly involved in p53 signaling and DNA damage response. The 25% neutron exposure also showed maximum enrichment of known neutron associated gene ontology terms reported in the previous studies. Analysis of upstream regulators of gene expression showed strong activation of TP53, SLC29A1, PDCD1 and suppression of ANLN, AURK and ANXA2 across all exposures. While AGT was exclusively activated by neutron specific exposures. We confirmed the expression of genes which showed increased expression as a function of increased neutron percentage using quantitative real-time RT-PCR which matched with the microarray data. Thus, the data in this current study clearly indicates that gene expression can be used to estimate the percentage of the neutron component in mixed neutron-photon exposures.

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Gene expression changes and DNA damage after ex vivo exposure of peripheral blood cells to variable CT photon spectra

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