Abstract
BackgroundIn the event of an improvised nuclear device detonation, the prompt radiation exposure would consist of photons plus a neutron component that would contribute to the total dose. As neutrons cause more complex and difficult to repair damage to cells that would result in a more severe health burden to affected individuals, it is paramount to be able to estimate the contribution of neutrons to an estimated dose, to provide information for those making treatment decisions.ResultsMice exposed to either 0.25 or 1 Gy of neutron or 1 or 4 Gy x-ray radiation were sacrificed at 1 or 7 days after exposure. Whole genome microarray analysis identified 7285 and 5045 differentially expressed genes in the blood of mice exposed to neutron or x-ray radiation, respectively. Neutron exposure resulted in mostly downregulated genes, whereas x-rays showed both down- and up-regulated genes. A total of 34 differentially expressed genes were regulated in response to all ≥1 Gy exposures at both times. Of these, 25 genes were consistently downregulated at days 1 and 7, whereas 9 genes, including the transcription factor E2f2, showed bi-directional regulation; being downregulated at day 1, while upregulated at day 7. Gene ontology analysis revealed that genes involved in nucleic acid metabolism processes were persistently downregulated in neutron irradiated mice, whereas genes involved in lipid metabolism were upregulated in x-ray irradiated animals. Most biological processes significantly enriched at both timepoints were consistently represented by either under- or over-expressed genes. In contrast, cell cycle processes were significant among down-regulated genes at day 1, but among up-regulated genes at day 7 after exposure to either neutron or x-rays. Cell cycle genes downregulated at day 1 were mostly distinct from the cell cycle genes upregulated at day 7. However, five cell cycle genes, Fzr1, Ube2c, Ccna2, Nusap1, and Cdc25b, were both downregulated at day 1 and upregulated at day 7.ConclusionsWe describe, for the first time, the gene expression profile of mouse blood cells following exposure to neutrons. We have found that neutron radiation results in both distinct and common gene expression patterns compared with x-ray radiation.
Highlights
In the event of an improvised nuclear device detonation, the prompt radiation exposure would consist of photons plus a neutron component that would contribute to the total dose
We have found that neutron radiation results in both distinct and common gene expression patterns compared with x-ray radiation
There have been a limited number of studies that have compared gene expression profiles in mice or human blood cells after exposures involving heavy ions and α-particles, the latter representing isotopes likely to be used in a radiological dispersal device [9]
Summary
In the event of an improvised nuclear device detonation, the prompt radiation exposure would consist of photons plus a neutron component that would contribute to the total dose. Most of the gene expression signatures for the purpose of radiation biodosimetry have been obtained in response to photon (γ- and x-rays) exposure. There have been a limited number of studies that have compared gene expression profiles in mice or human blood cells after exposures involving heavy ions and α-particles, the latter representing isotopes likely to be used in a radiological dispersal device [9]. Using human peripheral blood mononuclear cells, Chauhan et al [10] found that the gene expression profile induced by α-particle radiation was very similar to the x-ray responses, despite the fact that α-particles are characterized by a higher linear energy transfer coefficient compared with x-rays [11]. Comparison of α-particle and x-ray irradiation impact on human tumor and endothelial cells [12], as well as human epidermal keratinocytes [13] produced distinct gene expression profiles
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