title: Comparison of gene expression response to neutron and x-ray irradiation using mouse blood.
abstract: 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. 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.
  
  
  
  Mice 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.
  
  
  
  We 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.
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY, 10032, USA.
authors.forename: Constantinos G
authors.initials: CG
authors.lastname: Broustas
authors.affiliation: Radiological Research Accelerator Facility, Columbia University, Irvington, NY, 10533, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Radiological Research Accelerator Facility, Columbia University, Irvington, NY, 10533, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Harken
authors.affiliation: Radiological Research Accelerator Facility, Columbia University, Irvington, NY, 10533, USA.
authors.forename: Guy
authors.initials: G
authors.lastname: Garty
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY, 10032, USA. saa2108@cumc.columbia.edu.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Amundson
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism / Q000528:radiation effects; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D063990:Gene Ontology; D051379:Mice; D058977:Molecular Sequence Annotation; D009502:Neutrons; D011829:Radiation Dosage; D015203:Reproducibility of Results; D059467:Transcriptome; D014965:X-Rays
keywords: Gene expression; Microarrays; Neutron; Radiation biodosimetry; x-ray