title: 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.
authors.affiliation: Département des Effets Biologiques des Rayonnements (EBR), Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France.
authors.forename: Marco
authors.initials: M
authors.lastname: Valente
authors.affiliation: Département des Effets Biologiques des Rayonnements (EBR), Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France.
authors.forename: Josiane
authors.initials: J
authors.lastname: Denis
authors.affiliation: Département des Effets Biologiques des Rayonnements (EBR), Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France.
authors.forename: Nancy
authors.initials: N
authors.lastname: Grenier
authors.affiliation: Département des Effets Biologiques des Rayonnements (EBR), Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Arvers
authors.affiliation: Service des Laboratoires, Hôpital d'Instruction des Armées Desgenettes, Lyon, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Foucher
authors.affiliation: Département des Effets Biologiques des Rayonnements (EBR), Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France.
authors.forename: François
authors.initials: F
authors.lastname: Desangles
authors.affiliation: Département des Effets Biologiques des Rayonnements (EBR), Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Martigne
authors.affiliation: Département des Effets Biologiques des Rayonnements (EBR), Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Chaussard
authors.affiliation: Département des Effets Biologiques des Rayonnements (EBR), Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Drouet
authors.affiliation: Bundeswehr Institute of Radiobiology, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Abend
authors.affiliation: Département des Effets Biologiques des Rayonnements (EBR), Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Hérodin
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D005720:Gamma Rays; D006801:Humans; D007501:Iron / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D023421:Models, Animal; D010215:Papio; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D011834:Radiation Monitoring / Q000295:instrumentation / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014508:Urea / Q000097:blood; D014916:Whole-Body Irradiation / Q000009:adverse effects / Q000379:methods*
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; C084881:flt3 ligand protein; D014508:Urea; D002097:C-Reactive Protein; D007501:Iron; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase