Priority List of Research Areas for Radiological Nuclear Threat Countermeasures

Armed Forces Radiobiology Research Institute, Uniformed Services University, Bethesda, Maryland 20889-5603, USA.
Radiation Research (Impact Factor: 2.91). 02/2005; 163(1):115-23. DOI: 10.1667/RR3283
Source: PubMed


To help the nation prepare for the possibility of a terrorist attack using radiological and nuclear devices, the Office of Science and Technology Policy and the Homeland Security Council established an interagency working group. The working group deliberated on the research needs for radiological/ nuclear threat countermeasures and identified and prioritized 18 areas for further attention. The highest priorities were given to research on (1) radioprotectors for use prior to exposure; (2) therapeutic agents for postexposure treatment; (3) antimicrobial therapy for infections associated with radiation exposure; (4) cytokines and growth factors; (5) mechanisms of radiation injury at the molecular, cellular, tissue and organism levels; and (6) automation of biodosimetric assays. High priority was given to (1) developing biomarkers for biodosimetry; (2) enhancing training in the radiation sciences; (3) exploring the consequences of combined injury; (4) establishing a repository of information regarding investigational countermeasures; and (5) following the health of an exposed population to better prepare for subsequent events. The research areas that the committee felt required the attention of the radiation research community are described in this report in an effort to inform this community about the needs of the nation and to encourage researchers to address these critical issues.

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Available from: Terry Pellmar,
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    • "Several authors such as Lloyd et al. [4], Mettler and Voelz [10], Goans and Waselenko [11], Pellmar and Rockwell [12], and Coleman et al. [13], have reviewed in detail the need for cytogenetic biodosimetry to aid medical management of exposed subjects. Several others, Weber et al. [14], Schunk et al. [15], Martin et al. [16], Romm et al. [17], Garty et al. [18] and Fenech et al. [19], have described the need for automation of cytogenetic assays, such as DCA and/or CBMN (Cytokinesis-blocked micronucleus assay), in order to support medical management of accidentally exposed individuals. "
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    ABSTRACT: High-throughput individual diagnostic dose assessment is essential for medical management of radiation-exposed subjects after a mass casualty. Cytogenetic assays such as the Dicentric Chromosome Assay (DCA) are recognized as the gold standard by international regulatory authorities. DCA is a multi-step and multi-day bioassay. DCA, as described in the IAEA manual, can be used to assess dose up to 4–6 weeks post-exposure quite accurately but throughput is still a major issue and automation is very essential. The throughput is limited, both in terms of sample preparation as well as analysis of chromosome aberrations. Thus, there is a need to design and develop novel solutions that could utilize extensive laboratory automation for sample preparation, and bioinformatics approaches for chromosome-aberration analysis to overcome throughput issues. We have transitioned the bench-based cytogenetic DCA to a coherent process performing high-throughput automated biodosimetry for individual dose assessment ensuring quality control (QC) and quality assurance (QA) aspects in accordance with international harmonized protocols. A Laboratory Information Management System (LIMS) is designed, implemented and adapted to manage increased sample processing capacity, develop and maintain standard operating procedures (SOP) for robotic instruments, avoid data transcription errors during processing, and automate analysis of chromosome-aberrations using an image analysis platform. Our efforts described in this paper intend to bridge the current technological gaps and enhance the potential application of DCA for a dose-based stratification of subjects following a mass casualty. This paper describes one such potential integrated automated laboratory system and functional evolution of the classical DCA towards increasing critically needed throughput.
    Mutation Research/Genetic Toxicology and Environmental Mutagenesis 07/2015; 793. DOI:10.1016/j.mrgentox.2015.07.011 · 2.42 Impact Factor
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    • "Development of biomarker-based biodosimetry has been put forth as one of the key priority development areas for nuclear threat countermeasures [14], and microarray data/gene based profiling has served as timely and minimally invasive means to address this priority area [15]. There have been several studies examining the gene expression profiles of human cells using functional genomics platforms for photon radiation [16-18]. "
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    ABSTRACT: Background The 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. Methods Peripheral 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. Results Twenty-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. Conclusion Current gene panels for photon radiation may also be applicable for use in α-particle radiation biodosimetry.
    BMC Medical Genomics 07/2014; 7(1):43. DOI:10.1186/1755-8794-7-43 · 2.87 Impact Factor
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    • "These agents should help to treat patients and radiation victims exposed to high doses of ionizing radiation as a consequence of radiation accidents or radiological (nuclear) terrorist attacks [2] [3] [4] [5] [6]. The topic of " Therapeutic Agents (Postexposure Treatment) " has been given top priority in the Priority List of Research Areas for Radiological Nucelar Threat Countermeasures by Pellmar et al. [7]. "
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    ABSTRACT: Combined approaches to the treatment of acute radiation disease are preferred to single-agent therapies due to proven or anticipated better outcomes comprising increased therapeutic efficacy and decreased incidence of undesirable side effects. Our studies on post-exposure treatment of mice irradiated by sublethal or lethal doses of ionizing radiation included testing the effectiveness of meloxicam, a cyclooxygenase-2 inhibitor, and IB-MECA, an adenosine A3 receptor agonist. The efficacy of meloxicam and IB-MECA to positively influence the progress of the acute radiation disease has been tested in situations of their combined administration with granulocyte colony-stimulating factor (G-CSF) or with each other. The results of our studies revealed a significantly improved regeneration of hematopoietic cell populations ranging from the bone marrow progenitor cells to mature blood cells following combined treatments. Also, survival of mice exposed to lethal radiation doses was highest in the animals treated with a combination of the two drugs. It can be inferred from the results that if the drug combinations employed were used in humans, e.g. in the treatment of victims of radiation accidents, a better therapeutic outcome could be expected. Therefore, further studies directed at clinical applications of meloxicam and IB-MECA in radiation victims is recommended.
    Central European Journal of Biology 06/2014; 9(6). DOI:10.2478/s11535-014-0295-0 · 0.71 Impact Factor
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