Antibody-Based Screen for Ionizing Radiation-Dependent Changes in the Mammalian Proteome for Use in Biodosimetry

Ivey, Richard G.; Subramanian, Oby; Lorentzen, Travis D.; Paulovich, Amanda G.

doi:10.1667/rr1638.1

Cited by 15 publications

(11 citation statements)

References 36 publications

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“…This would also help in the timely reassurance of many individuals not requiring treatment (the “worried well”), who might otherwise overwhelm health resources. Several promising approaches to radiation biodosimetry have been pursued in the past few years, including automation or streamlining of classical cytogenetic assays (2, 3) and more recently, the development of proteomic (4, 5), transcriptomic (6–9) or metabolomic signatures (10, 11). The majority of such studies have focused on single acute exposures, but depending on the situation, protracted low-dose-rate (LDR) exposures (e.g., fallout or ground shine) may be expected to constitute much of the total dose.…”

Section: Introductionmentioning

confidence: 99%

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

et al. 2015

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In the event of a nuclear accident or radiological terrorist attack, there will be a pressing need for biodosimetry to triage a large, potentially exposed population and to assign individuals to appropriate treatment. Exposures from fallout are likely, resulting in protracted dose delivery that would, in turn, impact the extent of injury. Biodosimetry approaches that can distinguish such low-dose-rate (LDR) exposures from acute exposures have not yet been developed. In this study, we used the C57BL/6 mouse model in an initial investigation of the impact of low-dose-rate delivery on the transcriptomic response in blood. While a large number of the same genes responded to LDR and acute radiation exposures, for many genes the magnitude of response was lower after LDR exposures. Some genes, however, were differentially expressed (P < 0.001, false discovery rate < 5%) in mice exposed to LDR compared with mice exposed to acute radiation. We identified a set of 164 genes that correctly classified 97% of the samples in this experiment as exposed to acute or LDR radiation using a support vector machine algorithm. Gene expression is a promising approach to radiation biodosimetry, enhanced greatly by this first demonstration of its potential for distinguishing between acute and LDR exposures. Further development of this aspect of radiation biodosimetry, either as part of a complete gene expression biodosimetry test or as an adjunct to other methods, could provide vital triage information in a mass radiological casualty event.

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Section: Introductionmentioning

confidence: 99%

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

et al. 2015

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“…One study using irradiated human cell lines of hematological origin screened 161 individual proteins using Western blotting and identified 55 radiation-responsive proteins. The feasibility of applying these in vitro determined targets to a TBI canine model was also demonstrated, with a similar trend between in vitro and in vivo responses to radiation for an example target protein ( 27 ). Expression profiles of several individual protein biomarkers have been examined for their relationship to received radiation dose and exposure pattern.…”

Section: Proteomicsmentioning

confidence: 74%

State-of-the-Art Advances in Radiation Biodosimetry for Mass Casualty Events Involving Radiation Exposure

Sproull

Camphausen

2016

Radiation Research

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With the possibility of large-scale terrorist attacks around the world, the need for modeling and development of new medical countermeasures for potential future chemical, biological, radiological and nuclear (CBRN) has been well established. Project Bioshield, initiated in 2004, provided a framework to develop and expedite research in the field of CBRN exposures. To respond to large-scale population exposures from a nuclear event or radiation dispersal device (RDD), new methods for determining received dose using biological modeling became necessary. The field of biodosimetry has advanced significantly beyond this original initiative, with expansion into the fields of genomics, proteomics, metabolomics and transcriptomics. Studies are ongoing to evaluate the use of lymphocyte kinetics for dose assessment, as well as the development of field-deployable EPR technology. In addition, expansion of traditional cytogenetic assessment methods through the use of automated platforms and the development of laboratory surge capacity networks have helped to advance our biodefense preparedness. In this review of the latest advances in the field of biodosimetry we evaluate our progress and identify areas that still need to be addressed to achieve true field-deployment readiness.

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“…In contrast, immunoassays take only a few hours from sampling to final results, can be fully automated to process tens of thousands of samples at a time and provides simple numerical readouts that require little technical analysis. It is likely that multiple biomarkers will be needed to unambiguously identify any exposed individuals and the development of a complete proteome profile for irradiated cells will be important in developing an effective biodosimeter (Ivey et al 2009). Potentially, a suite of antibodies labelled with different fluorophores could simultaneously detect different antigens in the same assay, likely improving the level of sensitivity.…”

Section: Discussionmentioning

confidence: 99%

High-throughput antibody-based assays to identify and quantify radiation-responsive protein biomarkers

Chai

Zhou

Hei³

2010

International Journal of Radiation Biology

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Purpose After a radiological ‘dirty bomb’ incident in a major metropolitan center, substantial numbers of people may be exposed to radiation. However, only a fraction of those individuals will need urgent medical attention. Consequently, a rapid screening test is needed to identify those people who require immediate treatment. Material and methods Ten normal human cell lines were screened by enzyme-linked immunosorbent assay (ELISA) for the expression of a dozen secreted cytokines that have been reported to have changes in protein or mRNA levels at 1, 2, and 3 days after 0–10 Gy irradiation using 137Cs gamma rays at 0.82 Gy min−1. After this systematic in vitro screen, we measured changes in the level of a subset of these candidate proteins in plasma from irradiated C57BL/6 mice (n = 3 per group), comparing shams with a single radiation dose (5 Gy X-rays) at 3.7 Gy min−1 at 6 h after irradiation. Results We identified four cytokine molecules that had altered levels after radiation exposure, one of which, Interleukin (IL) 6, was consistently elevated after irradiation in vitro and in vivo. Conclusions Our findings underscore the potential for IL6 as a marker for an immunoassay-based, rapid, high-throughput biodosimeter.

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Antibody-Based Screen for Ionizing Radiation-Dependent Changes in the Mammalian Proteome for Use in Biodosimetry

Cited by 15 publications

References 36 publications

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

State-of-the-Art Advances in Radiation Biodosimetry for Mass Casualty Events Involving Radiation Exposure

High-throughput antibody-based assays to identify and quantify radiation-responsive protein biomarkers

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