Identification of differentially expressed genes and pathways in mice exposed to mixed field neutron/photon radiation
Autor: | Guy Garty, Constantinos G. Broustas, Sally A. Amundson, Andrew D. Harken |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male lcsh:QH426-470 lcsh:Biotechnology Ribosome biogenesis Biology Radiation Dosage 03 medical and health sciences Mice lcsh:TP248.13-248.65 Gene expression Genetics Relative biological effectiveness Animals Eukaryotic Small Ribosomal Subunit PI3K/AKT/mTOR pathway Oligonucleotide Array Sequence Analysis Neutrons eIF2 Photons X-Rays Translation (biology) Radiation biodosimetry Protein ubiquitination 3. Good health Cell biology Mice Inbred C57BL lcsh:Genetics 030104 developmental biology Gene Ontology Gene Expression Regulation Mouse blood Transcriptome Mixed field neutron/photon Metabolic Networks and Pathways Biotechnology Research Article Signal Transduction |
Zdroj: | BMC Genomics BMC Genomics, Vol 19, Iss 1, Pp 1-14 (2018) |
ISSN: | 1471-2164 |
Popis: | Background Radiation exposure due to the detonation of an improvised nuclear device remains a major security concern. Radiation from such a device involves a combination of photons and neutrons. Although photons will make the greater contribution to the total dose, neutrons will certainly have an impact on the severity of the exposure as they have high relative biological effectiveness. Results We investigated the gene expression signatures in the blood of mice exposed to 3 Gy x-rays, 0.75 Gy of neutrons, or to mixed field photon/neutron with the neutron fraction contributing 5, 15%, or 25% of a total 3 Gy radiation dose. Gene ontology and pathway analysis revealed that genes involved in protein ubiquitination pathways were significantly overrepresented in all radiation doses and qualities. On the other hand, eukaryotic initiation factor 2 (EIF2) signaling pathway was identified as one of the top 10 ranked canonical pathways in neutron, but not pure x-ray, exposures. In addition, the related mTOR and regulation of EIF4/p70S6K pathways were also significantly underrepresented in the exposures with a neutron component, but not in x-ray radiation. The majority of the changed genes in these pathways belonged to the ribosome biogenesis and translation machinery and included several translation initiation factors (e.g. Eif2ak4, Eif3f), as well as 40S and 60S ribosomal subunits (e.g. Rsp19, Rpl19, Rpl27). Many of the differentially downregulated ribosomal genes (e.g. RPS19, RPS28) have been causally associated with human bone marrow failure syndromes and hematologic malignancies. We also observed downregulation of transfer RNA processes, in the neutron-only exposure (p |
Databáze: | OpenAIRE |
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