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Thorax irradiation of Non-Human Primates induces persistent gene expression changes in blood cells.

ABSTRACT: In the current study, we investigated the gene expression response of blood cells of non-human primates that were whole thorax irradiated with a 10.1 Gy total dose. Partial irradiation of the NHP in the upper half of the body allows study of late radiation lung injury while avoiding acute respiratory syndromes related to hematopoietic and gastrointestinal injury. In this study, we report gene expression changes in the peripheral blood, an easily biopsied tissue, up to a month after radiation injury to the lungs. We isolated total RNA from peripheral blood at 3 days before irradiation, and then from the same animals on days 2, 5 and 30 after irradiation. Using Agilent Human Whole Genome microarrays, we identified 1187 genes that were significantly differentially expressed across the 30-day time course of this study. We identified common biological functions affected that persisted across the 30-day study, such as immune response. Response to oxygen-containing compounds and bacterial molecules were implicated by the gene expression changes at both the earliest day 2 and last, day 30 time-point and suggest that although cells are being recycled through the body in a 30-day time course after exposure to irradiation, the damage to blood cells and immunity, specifically the response to infections might persist throughout the study .

ORGANISM(S): Homo sapiens Macaca mulatta

PROVIDER: GSE84898 | GEO | 2018/01/01

SECONDARY ACCESSION(S): PRJNA335582

REPOSITORIES: GEO

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Project description:Background: Ionizing Radiation (IR) is a known pro-inflammatory agent and in the process of development of biomarkers for radiation biodosimetry a chronic inflammatory disease condition could act as a confounding factor. Hence, it is important to develop radiation biodosimetry that can distinguish between IR-induced inflammatory responses and pre-existing disease. In this study, we compared the gene expression response of a genetically modified mouse model of inflammatory bowel disease (Il10-/-) with that of a normal wild-type mouse to potentially develop transcriptomic based biodosimetry markers for individual susceptibility to radiation. Results: Wild-type (WT) and Il10-/- mice were exposed to whole body irradiation of 7Gy (LD50/30 for IL10-/-) X-rays. Gene expression responses were studied using high throughput whole genome microarrays in peripheral blood after 24h post-irradiation. Analysis resulted in identification of 1962 and 1844 genes differentially expressed (p < 0.001, FDR < 10%) after radiation exposure in Il10-/- and WT mice respectively. A set of 155 genes were also identified as differentially expressing between WT and Il10-/- mice at the baseline pre-irradiation level. Gene ontology analysis revealed that the baseline differentially expressing genes (155) were mainly involved in Inflammatory response, Glutathione metabolism and fibrosis. Analysis of radiation responsive genes revealed commonality of immune function genes between WT and Il10-/- mice. Gene ontology analysis revealed that innate immune response and p53 signaling processes were strongly associated with up-regulated genes whereas, B-cell development process was found to be significant amongst downregulated genes in response to radiation in the two genotypes. However, specific immune response pathways like MHC class I antigen presentation and response to viral/bacterial infection were particularly associated with radiation responsive genes of Il10-/- mice but not with WT mice. Further analysis of activation status of specific canonical pathways and upstream regulators using IPA-prediction tool revealed significant difference in the activation status of T-cell and hormone mediated signaling as well as regulators of inflammation between WT and Il10-/- after irradiation.

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Thorax irradiation of Non-Human Primates induces persistent gene expression changes in blood cells.

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