Serum Amyloid A as a Biomarker for Radiation Exposure

Abstract

There is a need for minimally invasive biomarkers that can accurately and quickly quantify radiation exposure. Radiation-responsive proteins have applications in clinical medicine and for mass population screenings after a nuclear or radiological incident where the level of radiation exposure and exposure pattern complicate medical triage for first responders. In this study, we evaluated the efficacy of the acute phase protein serum amyloid A (SAA) as a biomarker for radiation exposure using plasma from irradiated mice. Ten-week-old female C57BL6 mice received a 1–8 Gy single whole-body or partial-body dose from a Pantak X-ray source at a dose rate of 2.28 Gy/min. Plasma was collected by mandibular or cardiac puncture at 6, 24, 48 and 72 h or 1–3 weeks postirradiation. SAA levels were determined using a commercially available ELISA assay. Data was pooled to generate SAA μg/ml threshold values correlating plasma SAA levels with radiation dose. SAA levels were statistically significant over control at all exposures between 2 and 8 Gy at 24 h postirradiation but not at 6, 48 and 72 h or 1–3 weeks postirradiation. SAA levels at 1 Gy were not significantly elevated over control at all time points. Total-body-irradiated (TBI) SAA levels at 24 h were used to generate a dose prediction model that successfully differentiated TBI mice into dose received cohorts of control/1 Gy and ≥2 Gy groups with a high degree of accuracy in a blind study. Dose prediction of partial-body exposures based on the TBI model correlated increasing predictive accuracy with percentage of body exposure to radiation. Our findings indicate that plasma SAA levels might be a useful biomarker for radiation exposure in a variety of total- and partial-body irradiation settings.

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

“…FL is a cytokine known to induce proliferation and differentiation of bone marrow stem cells of myeloid and lymphoid origin and has recently been described as a biomarker of radiation exposure (3). The apolipoprotein SAA is a major acute phase reactant protein playing a central role in the inflammatory response and has been characterized as a marker of radiation exposure in heterogeneous radiation exposure profiles (4–6). MMP9 is active in extra-cellular matrix (ECM) degradation and FGB, the principle protein involved in clot formation, were also included in the study having been previously shown to be radiation responsive (4).…”

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

“…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 ).…”

“…The relationship between radiation injury and activation of the acute-phase response is also well established with correlations between CRP elevation and onset and severity of acute radiation syndrome (ARS) ( 4 ). Elevation of acute-phase proteins such as CRP and serum amyloid A (SAA) were also reported to increase in a dose-dependent manner after irradiation ( 25 , 26 ).…”

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

“…Frequency of occurrence of cells with dumbbell-shaped nuclei depends on the dose of irradiation and this correlation is described by a linearquadratic function with the following equation: y = 0.003+0.014x +0.005x 2 [31]. We would like to emphasize that the simplest biomarkers (nuclei abnormalities) we suggest for radiation exposure detection in vivo is not an alternative to classical radiation biomarkers in vitro [17], as well as to other modern approaches [2][3][4][5][44][45][46]. Detection of chromosomal aberrations (dicentrics) and the cytochalasine B micronucleus and "Cytome" methods are reliable bioindication and biodosimetry methods.…”

“…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].…”