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

Abstract

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.

Time‐Dependent Measurement of Nrf2‐Regulated Antioxidant Response to Ionizing Radiation Toward Identifying Potential Protein Biomarkers for Acute Radiation Injury

“…Despite continual risk of radiation from nuclear accidents and terrorist attacks, effective assessment of acute radiation exposure remains to be established for triage and treatment of the population . Following a radiological event, several stages of mass screening using a combination of physical and biological dosimetry methods will be needed to establish the severity of any radiation exposure.…”

“…Traditionally, clinical determination of radiation dose relies on cytogenetic assays such as chromosome aberration, which normally involves lymphocyte cell culture and scoring of abnormalities. This process is time consuming and requires experienced personnel, making it unsuitable for triage of a mass‐casualty event . In addition, cytogenetic assays from blood yields a crude total body dose estimate, which is not ideal given that accidental exposure is likely heterogeneous and there is considerable difference in organ sensitivities to radiation.…”

“…Despite continual risk of radiation from nuclear accidents and terrorist attacks, effective assessment of acute radiation exposure remains to be established for triage and treatment of the population. [1,2] Following a radiological event, several stages of mass screening using a combination of physical and biological dosimetry methods will be needed to establish the severity of any radiation exposure. Traditionally, clinical determination of radiation dose relies on cytogenetic assays such as chromosome aberration, which normally involves lymphocyte cell culture and scoring of abnormalities.…”

Metabolomic applications in radiation biodosimetry: exploring radiation effects through small molecules

“…In the case of radiation biodosimetry, an estimated 50,000 individuals will need to be evaluated within 2 to 6 days after a 10 kt bomb, according to military scenarios for planning (Flood et al, 2016a), although in a city such as New York, NY or Washington, DC the number may well be much higher. Complete blood count (CBC) differential for lymphocyte depletion kinetics, premature chromosome condensation (PCC), dicentric measurement, gene expression, γ-H2AX, cytokinesis block micronucleus assay (CBMN), protein biomarkers, metabolic biomarkers, and electron paramagnetic resonance (EPR) or optically stimulated luminescence (OSL) of teeth have been proposed as some of the methods for radiation biodosimetry (Amundson and Fornace, 2003, Brengues et al, 2010, Coy et al, 2011, Gruel et al, 2013, Lamadrid Boada et al, 2013, Sharma and Moulder, 2013, Sullivan et al, 2013, Xu et al, 2013, Hu et al, 2015, Flood et al, 2016b, Garty et al, 2016, Sproull and Camphausen, 2016). However, some of these assays require a significant length of time for processing and highly trained personnel to perform the assays and interpret the results.…”

Nuclear Abnormalities of Lymphocytes as the Simplest Markers for Bioindication Test in Case of Mass Casualty Events Involving Radiation Exposure

“…The field of activity of biodosimetry has significantly expanded with the methods of genomics [1,2], proteomics [3,4], metabolomics [5] and transcriptomics [6]. At the same time, methods of cytogenetics that require the cultivation of lymphocytes in vitro or the use of special equipment still remain the classical methods [7][8][9][10][11][12][13]. These include the dicentric chromosome assay (DCA), the micronucleus assay or cytokinesis-block micronucleus assay (CBMN), the premature chromosome condensation assay (PCC), fluorescence in situ hybridization (FISH) and the recent addition of cH2AX scoring as a cytogenetic tool.…”