Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model

Abstract

Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

Identification of Potential Radiation Responsive Metabolic Biomarkers in Plasma of Rats Exposed to Different Doses of Cobalt-60 Gamma Rays

“…13,14 Metabolomics based on mass spectrometry (MS) platforms has shown great potential to explore the biomarkers of radiation damage due to high-throughput and minimally invasive sample collection methods. 15,16 Over the last decade, metabolomics studies have been conducted using rodent, 17,18 non-human primates, 19,20 and humans 21,22 to explore IR-induced potential biomarkers. These studies have confirmed a large number of metabolites are altered after exposure to IR.…”

Candidate protein markers for radiation biodosimetry in the hematopoietically humanized mouse model

“…Few studies have systematically validated radio-responsive human protein markers in vivo for dose- and time-response after radiation exposure. Radiation responsive plasma proteins such as Flt3 ligand (Flt3L), serum amyloid A (SAA) and Interleukin-6 (IL-6) have been studied in mouse models as markers of acute radiation syndrome and radiation exposure up to a week 10 , 11 . Using the NHP model, C-reactive protein (CRP), SAA, IL-6, Flt3L protein biomarkers expressed in NHP plasma have been proposed as early indicators of dose assessment and radiation-induced injury up to ~7 days post irradiation 12 , 13 .…”

Early metabolic characterization of brain tissues after whole body radiation based on gas chromatography–mass spectrometry in a rat model

“…However, single‐dose assessment is not sufficient to provide information on organ injury. Whole‐body or partial‐body irradiation with high doses can result in the acute radiation syndrome and multiple organ dysfunction syndrome (Ossetrova, Ney, Condliffe, Krasnopolsky, & Hieber, ; Roy et al, ), both of which are related to organ injury. In addition, radiation doses in the body are usually inhomogeneous in radiation accidents.…”