title: Hematopoietic radiation syndrome in the Gottingen minipig.
abstract: Additional large animal models for the acute radiation syndrome (ARS) would facilitate countermeasure development. We demonstrate here that Gottingen minipigs develop hematopoietic ARS symptoms similar to those observed in canines, non-human primates (NHPs) and humans. Dosimetry for whole-body γ irradiation (0.6 Gy/min) was performed using electronic paramagnetic resonance (EPR) with alanine; National Institute of Standards and Technology (NIST)-calibrated alanine pellets and water-filled Plexiglas phantoms were used. After irradiations of 1.6-2.0 Gy, blood pancytopenia was observed for several weeks, accompanied by the characteristic ARS stages: prodromal symptoms, latent period, illness and recovery or morbidity. Morbidity occurred between days 14 and 27, with a preliminary LD(50/30) estimate between 1.7 and 1.9 Gy. The criterion of whether platelet counts were <200 × 10(3)/µl 7 days postirradiation predicted whether animals would survive in 18 out of 20 cases. The degree of granulocytosis 3 h postirradiation was inversely correlated with survival. Animals euthanized based on preset morbidity criteria displayed signs of multi-organ dysfunction, including widespread internal hemorrhage and alterations in organ function reflected in blood chemistry. Circulating C-reactive protein (CRP), a marker for inflammation, became elevated within hours after irradiation, subsided after several days, and increased again after 14 days. The results support further development of the Gottingen minipig as a model for ARS.
authors.affiliation: Radiation Countermeasures Program, Scientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889-5603, USA. moroni@afrri.usuhs.mil
authors.forename: Maria
authors.initials: M
authors.lastname: Moroni
authors.forename: Thea V
authors.initials: TV
authors.lastname: Coolbaugh
authors.forename: Eric
authors.initials: E
authors.lastname: Lombardini
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Mitchell
authors.forename: Krinon D
authors.initials: KD
authors.lastname: Moccia
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Shelton
authors.forename: Vitaly
authors.initials: V
authors.lastname: Nagy
authors.forename: Mark H
authors.initials: MH
authors.lastname: Whitnall
mesh_terms: D054508:Acute Radiation Syndrome / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D019963:Clinical Chemistry Tests; D004195:Disease Models, Animal; D006405:Hematology; D006410:Hematopoiesis / Q000528:radiation effects*; D006801:Humans; D008297:Male; D016019:Survival Analysis; D013552:Swine
chemical_list: D002097:C-Reactive Protein