Further biodosimetry investigations using murine partial-body irradiation model

Abstract

This study evaluates both the effects of physical restraint and use of candidate biomarkers in a CD2F1 male mouse partial-body irradiation model for biological dosimetry diagnostic assays. Mice were irradiated (6-Gy, 250-kVp X ray) to 3/3rd (total body), 2/3rd (gut and torso), 1/3rd (gut only) and 0/3rd (sham) of total body. Blood was sampled for haematology and blood plasma proteomic biomarkers at 1 and 2 d after exposure. Increases in the body fraction exposed showed progressive decreases in lymphocyte counts and increases in the neutrophil-to-lymphocyte ratios with no significant differences in the neutrophil and platelet counts. The radioresponse for plasma biomarker Flt3L showed proportional increases; however, G-CSF and SAA levels exhibited dramatic and non-proportional increases in levels. Physical restraint at 1 d post-exposure increased lymphocyte counts and SAA, decreased neutrophil-to-lymphocyte ratio and Flt3L and showed no effects on neutrophil and platelet counts or G-CSF.

Detection of Acute Radiation Sickness: A Feasibility Study in Non-Human Primates Circulating miRNAs for Triage in Radiological Events

“…On the other hand, miR-150-5p shows a dose-dependent decrease in abundance in all days, with strong decreases occurring in day 3 and 7 (Fig 3A). Many of these miRNA sequences display tissue-specific expression profiles, suggesting that miRNA profiles may be able to distinguish which tissues were affected by partial body exposure to ionizing radiation, a major unmet need in radiation exposure and triage planning (Fig 3B) [2,5]. WBI caused both increase and decrease in apparent abundance of circulating miRNA.…”

“…As such, ARS in humans follows a deterministic path whereby dose effects have distinct clinical outcomes: generally less than 2 Gy exhibit mild symptoms and hematological effects are prominent at doses between 2 and 6 Gy and progress slowly. Gastrointestinal effects are prominent at doses greater than 5–6 Gy and progress more rapidly, while neurovascular collapse ensues at doses greater than 10–20 Gy which occurs immediately [2,3]. Rapid and early diagnosis is essential as demonstrated by the dramatic increase in survival rates if treatments are administered within few days after exposure [4,5].…”

“…The gold standard dicentric chromosome (DC) assay in lymphocytes is highly technical and labor intensive, and is unlikely to be a viable for early triage [11]. Metabolites and several protein markers, such as C-reactive protein, amylase, and cytokines, have been investigated for their potential as biodosimeters [2–5,12,13]. However, inability to determine organ specific damage and fluctuations due to common differences in genetic and immune responses affect the readout, especially during partial body exposure to ionizing radiation.…”

Multivariate Analysis of Radiation Responsive Proteins to Predict Radiation Exposure in Total-Body Irradiation and Partial-Body Irradiation Models

“…FL and SAA have also been previously characterized in other biodosimetry studies modeling total-body irradiation (TBI) and partial-body irradiation (PBI) (5, 8–10). In the current study, this combination of proteins was evaluated for its efficacy in predicting received dose in plasma from total-body and partial-body irradiated mice.…”

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

“…Similar changes in expression were seen in plasma for SAA, FL, IL6 and G-CSF in TBI mice models ( 31 – 33 ). Partial-body exposures have also been shown to correlate with plasma expression of SAA, FL and G-CSF using a murine model ( 34 , 35 ). These studies were able to show relative increases in expression of plasma biomarkers correlating to an increasing area of partial-body exposure ( 26 , 36 ).…”