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Radiation responses in peripheral white blood cells of smokers and non-smokers

ABSTRACT: Understanding the possible impact of potential confounding factors is necessary for any approach to radiation biodosimetry. Potential confounding factors have not been fully addressed for gene expression-based biodosimetry approaches, such as we are developing. To begin addressing this need, we have used an ex vivo irradiated peripheral blood cell model to investigate the potential effect of smoking on the global radiation gene expression response, and looked for genes that respond to radiation differently in smokers and non-smokers, and also in males and females. The results indicate that only a small number of genes may be significantly confounded by either factor, supporting the idea of developing peripheral blood gene expression strategies for radiation biodosimetry.

ORGANISM(S): Homo sapiens

PROVIDER: GSE23515 | GEO | 2011/03/16

SECONDARY ACCESSION(S): PRJNA131087

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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Radiation responses in peripheral white blood cells of smokers and non-smokers

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