Effects of alpha particle radiation on gene expression in human pulmonary epithelial cells

Chauhan, Vinita; Howland, Matthew; Mendenhall, Amy; O’Hara, Shifawn; Stocki, T. J.; McNamee, James P.; Wilkins, Ruth

doi:10.1016/j.ijheh.2012.04.004

Cited by 29 publications

(19 citation statements)

References 66 publications

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“…Transcriptomic datasets from a variety of human‐derived cell lines exposed to alpha particle radiation [Chauhan et al, ; Chauhan and Howland, ] were used to identify cell‐line specific similarities/differences in BMD modeling. A summary of the BMD outputs is provided in Figure and Table .…”

Section: Resultsmentioning

confidence: 99%

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Transcriptional benchmark dose modeling: Exploring how advances in chemical risk assessment may be applied to the radiation field

Chauhan

Kuo

McNamee

et al. 2016

Environ and Mol Mutagen

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Recent advances in “‐omics” technologies have simplified capacity to concurrently assess expression profiles of thousands of targets in a cellular system. However, compilation and analysis of “omics” data in support of human health protection remains a challenge. Benchmark dose (BMD) modeling is currently being employed in chemical risk assessment to estimate acceptable levels of exposure. Although typically applied to conventional endpoints, newer software has enabled this application to be extended to transcriptomic datasets. BMD analytical tools now have the capacity to model transcriptional dose‐response data to derive meaningful BMD values for genes, pathways and gene ontologies. In this report, radiation data obtained from the Gene Expression Omnibus (GEO) were analyzed to generate BMD values for transcriptional responses. The datasets comprised microarray analyses of human blood gamma‐irradiated ex vivo (0–20 Gy) and human‐derived cell lines exposed to alpha particle radiation (0.5–1.5 Gy). The distributions of BMDs for statistically significant genes and pathways in response to radiation exposure were examined and compared across studies. BMD modeling could identify pathway/gene sensitivities across wide radiation dose ranges, experimental conditions (time‐points, cell types) and radiation qualities. BMD analysis offered a new approach to examine transcriptional data. The results were shown to provide information on transcriptional thresholds of effects to support refined risk assessments for low dose ionizing radiation exposures, derive gene‐based values for relative biological effectiveness and identify pathways involved in radiation sensitivities across cell types which may extend to applications a clinical setting. Environ. Mol. Mutagen. 57:589–604, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 99%

“…Human lung fibroblasts are isolated from normal adult lung tissue. For all cell types the expression of TP53 has been observed with radiation exposure, however, the responses vary with cell‐type (Chauhan et al, ; Chauhan and Howland, ).…”

Section: Methodsmentioning

confidence: 99%

Transcriptional benchmark dose modeling: Exploring how advances in chemical risk assessment may be applied to the radiation field

Chauhan

Kuo

McNamee

et al. 2016

Environ and Mol Mutagen

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“…Monocytes (THP-1 cell line) expressed reduced levels of the activating factors IL-15, IL-17, macrophage inflammatory protein 1β (MIP-1β, also known as CCL3) and IL-2 as well as increased levels of Treg-attracting IP-10 [CXCL10 (104)], Rantes (CCL5) and immunosuppressive VEGF (105) 24 h after irradiation with 1.5 Gy α-particles ( 241 Am Source, LET 127 keV/µm) (106). Irradiation of THP-1 derived macrophages with 0.5–20 Gy carbon ions (18.3 MeV/n, LET 108 keV/µm) has been shown to result in decreased TNF-α and IL-6 expression.…”

Section: Cytokines and Chemokinesmentioning

confidence: 99%

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

Diegeler

Hellweg

2017

Front. Immunol.

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Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

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“…However, the availability of similar gene tools for high LET radiation types, such as α-particles, remains limited. To date, the majority of α-particle transcriptional studies have been performed in vitro using transformed or normal cell types [19-21]. There has also been a selected few studies that have profiled genomic changes and compared the responses following exposure of cells to different radiation types [22,23].…”

Section: Introductionmentioning

confidence: 99%

Identification of gene-based responses in human blood cells exposed to alpha particle radiation

2014

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BackgroundThe threat of a terrorist-precipitated nuclear event places humans at danger for radiological exposures. Isotopes which emit alpha (α)-particle radiation pose the highest risk. Currently, gene expression signatures are being developed for radiation biodosimetry and triage with respect to ionizing photon radiation. This study was designed to determine if similar gene expression profiles are obtained after exposures involving α-particles.MethodsPeripheral blood mononuclear cells (PBMCs) were used to identify sensitive and robust gene-based biomarkers of α-particle radiation exposure. Cells were isolated from healthy individuals and were irradiated at doses ranging from 0-1.5 Gy. Microarray technology was employed to identify transcripts that were differentially expressed relative to unirradiated cells 24 hours post-exposure. Statistical analysis identified modulated genes at each of the individual doses.ResultsTwenty-nine genes were common to all doses with expression levels ranging from 2-10 fold relative to control treatment group. This subset of genes was further assessed in independent complete white blood cell (WBC) populations exposed to either α-particles or X-rays using quantitative real-time PCR. This 29 gene panel was responsive in the α-particle exposed WBCs and was shown to exhibit differential fold-changes compared to X-irradiated cells, though no α-particle specific transcripts were identified.ConclusionCurrent gene panels for photon radiation may also be applicable for use in α-particle radiation biodosimetry.

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Effects of alpha particle radiation on gene expression in human pulmonary epithelial cells

Cited by 29 publications

References 66 publications

Transcriptional benchmark dose modeling: Exploring how advances in chemical risk assessment may be applied to the radiation field

Transcriptional benchmark dose modeling: Exploring how advances in chemical risk assessment may be applied to the radiation field

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

Identification of gene-based responses in human blood cells exposed to alpha particle radiation

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