title: Multiple parameter radiation injury assessment using a nonhuman primate radiation model-biodosimetry applications.
abstract: There are urgent needs to establish capability to rapidly assess radiation injury in mass casualty and population monitoring scenarios. This study's objective was to evaluate several currently available biomarkers that can provide early diagnostic triage information after radiation exposure. Hematology and blood chemistry measurements were performed on samples derived from a nonhuman primate (Macaca mulatta; n = 8) total-body irradiation (TBI) model (6.5-Gy Co gamma rays at 0.6 Gy min). The results from this study demonstrate: a) time course for changes in C-reactive protein (CRP) (-2 d to 15 d after TBI); b) time-dependent (-2 d, 1-4 d after TBI) changes in blood cell counts [i.e., lymphocytes decrease to 5-8% of pre-study levels at 1 to 4 d after TBI; ratio of neutrophil to lymphocytes increases by 44 +/- 18 (p = 0.016), 12 +/- 4 (p = 0.001), 8 +/- 2 (p = 0.0020), and 5.0 +/- 2 (p = 0.002) fold at 1, 2, 3, and 4 days after TBI, respectively]; and c) 4.5 +/- 0.8 (p = 0.002)-fold increases in serum amylase activity 1 d after TBI. Plasma CRP levels at 1 d after exposure were 22 +/- 13 (p = 0.0005) (females) and 44 +/- 11 (p = 0.0004) (males)-fold elevated above baseline levels. One hundred percent successful separation of samples from exposed macaques (24 h after TBI) vs. samples from the same macaque taken before irradiation using a discriminant analysis based on four biomarkers (i.e., lymphocytes, neutrophils, ratio of neutrophils to lymphocytes, and serum amylase activity) was demonstrated. These results demonstrate the practical use of multiple parameter biomarkers to enhance the discrimination of exposed vs. non-exposed individuals and justify a follow-on rhesus macaque dose-response study.
authors.affiliation: Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Blakely
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Ossetrova
authors.forename: Mark H
authors.initials: MH
authors.lastname: Whitnall
authors.forename: David J
authors.initials: DJ
authors.lastname: Sandgren
authors.forename: Vadim I
authors.initials: VI
authors.lastname: Krivokrysenko
authors.forename: Alexander
authors.initials: A
authors.lastname: Shakhov
authors.forename: Elena
authors.initials: E
authors.lastname: Feinstein
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D015415:Biomarkers / Q000097:blood*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008954:Models, Biological; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000097:blood* / Q000175:diagnosis*; D011874:Radiometry / Q000379:methods*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers