Radiation metabolomics and its potential in biodosimetry

Coy, Stephen L.; Cheema, Amrita K.; Tyburski, John B.; Laiakis, Evagelia C.; Collins, Sean P.; Fornace, Albert J.

doi:10.3109/09553002.2011.556177

Cited by 87 publications

(92 citation statements)

References 95 publications

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“…Human Metabolome database (http://www.hmdb.ca/), Madison Metabolomics Consortium Database (http://mmcd.nmrfam.wisc.edu/), METLIN Metabolite Database (http://metlin.scripps.edu/) -are available [227]. Metabolomics methodologies which mainly involve chromatography and mass spectrometry-based techniques, have been recently reviewed elsewhere [228]. Because metabolites result from the interactions between several complex cellular networks, metabolomics can provide a qualitative and quantitative overview of the global perturbations induced by IR in cells and biological fluids.…”

Section: Metabolites and Metabolomicsmentioning

confidence: 99%

Ionizing radiation biomarkers for potential use in epidemiological studies

Pernot

Hall

Baatout

et al. 2012

Mutation Research/Reviews in Mutation Research

196

153

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Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100mSv and/or 0.1mSvmin(-1)) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential.

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Section: Metabolites and Metabolomicsmentioning

confidence: 99%

Ionizing radiation biomarkers for potential use in epidemiological studies

Pernot

Hall

Baatout

et al. 2012

Mutation Research/Reviews in Mutation Research

196

153

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“…Another type of biological assay detects the presence of products produced by the pathways to carry out the responses to radiation damage, such as proteins (proteomics) (Marchetti et al 2006). Some assays detect the presence of small molecules that are produced directly by the radiation or, more typically, the metabolic products resulting from the damaged molecules (metabolomics) (Coy et al 2011). Alternatively, assays can assess indicators produced during the process of repair, especially those related to deoxyribonucleic acid (DNA) like 8-hydroxyguanine or fragments of DNA (γ-H2AX) (Avondoglio 2009;Rothkamm et al 2013).…”

Section: Biologically Based Biodosimetry (Other Than Responses Specifmentioning

confidence: 99%

Comparison of the Needs for Biodosimetry for Large-scale Radiation Events for Military versus Civilian Populations

Swartz

Flood

Williams³

et al. 2014

Health Physics

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The aim of this paper is to compare and contrast the needs for biodosimetry for initial triage for military forces and civilian populations when there are radiation exposures that involve potentially a large number of persons. Several differences in the likely scenarios for exposure of military forces include a greater likelihood of having higher rates of significant exposures, inhomogeneous exposures, significant doses from neutrons, and combined injury. Measurements will be able to begin sooner than for exposures in civilian settings because medical facilities usually are an integral part of the way military forces are deployed. It also will be very feasible to have personnel that will be trained and equipped specifically for rapid deployment to assess dose. As a consequence, the most appropriate biodosimetry techniques will include features that are not present or are less important for civilian settings; i.e., the need for changes that become measureable very soon after the radiation is received, the ability to complete measurements in very close proximity to the subjects (so samples do not need to be transported out and results returned), increased capability of resolving homogeneity of the exposure, ability to be carried out in an injured person, capability of determining whether neutrons have made a significant contribution to dose, and the ability to rely on more sophisticated equipment and trained personnel to carry out the measurements at the point of care.

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“…Similarly, the assessment of micronuclei have provided another measurable biodosimetry end point (17). Other end points include phosphorylation of histone, H2AX (18,19), electron paramagnetic resonance (20,21), protein expression (22)(23)(24)(25), metabolites (26)(27)(28) and gene expression levels (29)(30)(31)(32)(33)(34)(35). These methods have all shown promise to predict exposure dose, but also have limitations.…”

Section: Biodosimetrymentioning

confidence: 99%

Intragenic Controls Utilizing Radiation-Induced Alternative Transcript Regions Improves Gene Expression Biodosimetry

Forrester

Sprung

2014

Radiation Research

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Ionizing-radiation exposure can be life threatening if given to the whole body. In addition, whole body radiation exposure can affect large numbers of people such as after a nuclear reactor accident, a nuclear explosion or a radiological terrorist attack. In these cases, an accurate biodosimeter is essential for triage management. One of the problems for biodosimetry in general is the interindividual variation before and after exposure, which can make it challenging to assign an accurate dose. To begin to address this challenge, lymphocyte cell lines were exposed to 0, 1, 2 and 5 Gy ionizing radiation from a ¹³⁷Cs source at a dose rate of 0.6 Gy/min. Alternative transcripts with regions showing large differential responses to ionizing radiation were determined from exon array data. Gene expression analysis was then performed on isolated mRNA using qRT-PCR with normalization to intergenic (PGK1, GAPDH) and novel intragenic regions for candidate radiation-responsive genes, PPM1D and MDM2. Our studies show that the use of a cis-associated expression reference improved the potential dose prediction approximately 2.3-8.3 fold and provided an advantage for dose prediction compared to distantly or trans-located control ionizing radiation nonresponsive genes. This approach also provides an alternative gene expression normalization method to potentially reduce interindividual variations when untreated basal gene expression levels are unavailable. Using associated noninduced regions of ionizing radiation-induced genes provides a way to estimate basal gene expression in the irradiated sample. This strategy can be utilized as a biodosimeter on its own or to enhance other gene expression candidates for biodosimetry. This normalization strategy may also be generally applicable for other quantitative PCR strategies where normalization is required for a particular response.

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Radiation metabolomics and its potential in biodosimetry

Cited by 87 publications

References 95 publications

Ionizing radiation biomarkers for potential use in epidemiological studies

Ionizing radiation biomarkers for potential use in epidemiological studies

Comparison of the Needs for Biodosimetry for Large-scale Radiation Events for Military versus Civilian Populations

Intragenic Controls Utilizing Radiation-Induced Alternative Transcript Regions Improves Gene Expression Biodosimetry

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