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

PLoS One. 2015 Jul 15;10(7):e0132194. doi: 10.1371/journal.pone.0132194. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood*
  • C-Reactive Protein / metabolism
  • Creatine Kinase / blood
  • Gamma Rays
  • Humans
  • Iron / blood
  • Leukocyte Count
  • Male
  • Membrane Proteins / blood
  • Models, Animal*
  • Papio
  • Radiation Dosage
  • Radiation Injuries, Experimental / blood*
  • Radiation Injuries, Experimental / diagnosis
  • Radiation Injuries, Experimental / etiology
  • Radiation Monitoring / instrumentation
  • Radiation Monitoring / methods
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Urea / blood
  • Whole-Body Irradiation / adverse effects
  • Whole-Body Irradiation / methods*

Substances

  • Biomarkers
  • Membrane Proteins
  • flt3 ligand protein
  • Urea
  • C-Reactive Protein
  • Iron
  • Aspartate Aminotransferases
  • Creatine Kinase

Grant support

Financial support was provided by the French Ministry of Defense.