Abstract
In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI) and partial-body irradiation (PBI) to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS) and need hematologic support (i.e., mostly TBI victims). To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18) were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI) or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI). More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6) and PBI (n = 12), for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.
Highlights
Exposure to a nuclear or radiological (NR) event would lead to a heterogeneous population, with different radiation doses and degrees of shielding
In addition to dicentric chromosome assay (DIC) assessment, we investigated a large panel of biomarkers that could be evaluated with field capabilities following a nuclear or radiological event, such as absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), monocyte count (MONO), platelet count (PLT), hemoglobin (Hb), aspartate aminotransferase (AST), creatine kinase (CK), lactico dehydrogenase (LDH), urea, Flt-3 Ligand, iron, and C-reactive protein (CRP) level
Body dosimetry showed an average gradient of dose distribution front-to-back equal to 2.9 for both total-body irradiation (TBI) and the exposed side of partial-body irradiation (PBI)
Summary
Exposure to a nuclear or radiological (NR) event would lead to a heterogeneous population, with different radiation doses and degrees of shielding. The effectiveness of the medical care that follows depends on early triage and diagnosis of the victims to separate the “worried well” from the irradiated victims, especially in case of a large scale event. The discrimination between TBI and PBI patients is of vital importance as they will have a different clinical outcome. Medical management relies on physical, clinical and biological dosimetry. In accidental or malevolent situations, physical dosimeters would not be worn. Clinical signs and symptoms would be the main tools for early triage [1]. There is a need of easy-to-use biomarkers to improve medical management at the different phases of clinical evolution
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