Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation

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.

Pre-Exposure Gene Expression in Baboons with and without Pancytopenia after Radiation Exposure

“…Two baboons were exposed to 5 Gy TBI and two others to 2.5 Gy TBI. Eight different exposure patterns were simulated and two baboons were exposed per pattern which summed up to 16 baboons receiving PBI (for details see [28]) corresponding to an equivalent TBI dose of 2.5 or 5 Gy (Table 1). Two dose rates were used (8 cGy/min for 5 Gy TBI and 5 Gy 50% PBI, and 32 cGy/min for all other situations) because the Cobalt 60 source was changed during this study.…”

“…The mid-line tissue (right anterior iliac crest) dose in air was measured with an ionization chamber. Delivered doses were controlled by alumina powder thermoluminescent dosimeters placed on different cutaneous areas (thorax, thoracic and lumbar vertebrae, head, tibia, femur, femoral head, for details see [28]). The different exposure patterns chosen appeared in particular of significance when considering terrorist exposure or space travel where the nonuniform and heterogeneous exposure is relevant.…”

MicroRNA Expression for Early Prediction of Late Occurring Hematologic Acute Radiation Syndrome in Baboons

“…Time in restraint chairs was acceptable under conditions of the experiment and animal behaviour was monitored during irradiation using a video camera. In order to attain different patterns of PBI, a 20 cm thick lead screen was used to shield different parts of the body as detailed in [16]. Two baboons were exposed to 5 Gy TBI and two others to 2.5 Gy TBI.…”

“…Two baboons were exposed to 5 Gy TBI and two others to 2.5 Gy TBI. Eight different exposure patterns were simulated and two baboons were exposed per pattern which summed up to 16 baboons receiving PBI (for details see [16]) corresponding to an equivalent TBI dose of 2.5 or 5 Gy. Two dose rates were used (8 cGy/min for 5 Gy TBI and 5 Gy 50% PBI, and 32 cGy/min for all other situations) because the Cobalt 60 source was changed during this study.…”

“…The mid-line tissue (right anterior iliac crest) dose in air was measured with an ionization chamber. Delivered doses were controlled by alumina powder thermoluminescent dosimeters placed on different cutaneous areas (thorax, thoracic and lumbar vertebrae, head, tibia, femur, femoral head, for details see [16]). Since animals were exposed using either partial or total body irradiation (for details see [15] this resulted in whole body equivalent doses of 0 Gy for H0° HARS (blood samples taken before irradiation) and 2.5–5 Gy for baboons developing a mild H1-2° HARS disease and the same dose range of 2.5–5.0 Gy was observed for baboons developing a more aggravated H2-3° HARS disease (Table 1).…”