Abstract
BackgroundThe threat of a terrorist-precipitated nuclear event places humans at danger for radiological exposures. Isotopes which emit alpha (α)-particle radiation pose the highest risk. Currently, gene expression signatures are being developed for radiation biodosimetry and triage with respect to ionizing photon radiation. This study was designed to determine if similar gene expression profiles are obtained after exposures involving α-particles.MethodsPeripheral blood mononuclear cells (PBMCs) were used to identify sensitive and robust gene-based biomarkers of α-particle radiation exposure. Cells were isolated from healthy individuals and were irradiated at doses ranging from 0-1.5 Gy. Microarray technology was employed to identify transcripts that were differentially expressed relative to unirradiated cells 24 hours post-exposure. Statistical analysis identified modulated genes at each of the individual doses.ResultsTwenty-nine genes were common to all doses with expression levels ranging from 2-10 fold relative to control treatment group. This subset of genes was further assessed in independent complete white blood cell (WBC) populations exposed to either α-particles or X-rays using quantitative real-time PCR. This 29 gene panel was responsive in the α-particle exposed WBCs and was shown to exhibit differential fold-changes compared to X-irradiated cells, though no α-particle specific transcripts were identified.ConclusionCurrent gene panels for photon radiation may also be applicable for use in α-particle radiation biodosimetry.
Highlights
The threat of a terrorist-precipitated nuclear event places humans at danger for radiological exposures
DNA damage To ensure that the white blood cell (WBC) suspensions were undergoing irradiation and sustaining DNA damage, a biological assay indicative of DNA damage, the phosphorylation of H2AX, was employed
A bi-modal shaped curve was observed at the lowest dose of α-particle radiation which with increasing doses transitioned to a mono-modal curve
Summary
The threat of a terrorist-precipitated nuclear event places humans at danger for radiological exposures. A further 18 of these involved plutonium or highly enriched uranium Such events highlight the potential for radioactive material to fall into the wrong hands and potentially being used for the fabrication of a radiological dispersal device (RDD) [2]. Α-particles produce more significant biological effects when compared to equal absorbed doses from low-LET photon radiation, which are more sparsely ionizing [11,12,13]. This difference in ionization density may provide a means of distinguishing radiation type based on the magnitude of the biological response
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