Early-response biomarkers for assessment of radiation exposure in a mouse total-body irradiation model.
Nuclear accidents or terrorist attacks could expose large numbers of people to ionizing radiation. Early biomarkers of radiation injury will be critical for triage, treatment, and follow-up of such individuals. The authors evaluated the utility of multiple blood biomarkers for early-response assessment of radiation exposure using a murine (CD2F1, males) total-body irradiation (TBI) model exposed to ⁶⁰Co γ rays (0.6 Gy min⁻¹) over a broad dose range (0-14 Gy) and timepoints (4 h-5 d). Results demonstrate: 1) dose-dependent changes in hematopoietic cytokines: Flt-3 ligand (Flt3L), interleukin 6 (IL-6), granulocyte colony stimulating factor (G-CSF), thrombopoietin (TPO), erythropoietin (EPO), and acute phase protein serum amyloid A (SAA); 2) dose-dependent changes in blood cell counts: lymphocytes, neutrophils, platelets, and ratio of neutrophils to lymphocytes; 3) protein results coupled with peripheral blood cell counts established very successful separation of groups irradiated to different doses; and 4) enhanced separation of dose was observed as the number of biomarkers increased. Results show that the dynamic changes in the levels of SAA, IL-6, G-CSF, and Flt3L reflect the time course and severity of acute radiation syndrome (ARS) and may function as prognostic indicators of ARS outcome. These results also demonstrate proof-in-concept that plasma proteins show promise as a complimentary approach to conventional biodosimetry for early assessment of radiation exposures and, coupled with peripheral blood cell counts, provide early diagnostic information to manage radiation casualty incidents effectively, closing a gap in capabilities to rapidly and effectively assess radiation exposure early, especially needed in case of a mass-casualty radiological incident.
*Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University of the Health Sciences (USUHS), 8901 Wisconsin Avenue, Bethesda, MD 20889-5603.
Natalia I
NI
Ossetrova
Donald P
DP
Condliffe
Patrick H
PH
Ney
Katya
K
Krasnopolsky
Kevin P
KP
Hieber
Arifur
A
Rahman
David J
DJ
Sandgren
D000818:Animals; D015415:Biomarkers / Q000097:blood; D003037:Cobalt Radioisotopes / Q000009:adverse effects; D016207:Cytokines / Q000097:blood; D005720:Gamma Rays / Q000009:adverse effects; D006410:Hematopoiesis / Q000528:radiation effects; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000528:radiation effects; D011834:Radiation Monitoring / Q000379:methods*; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D015415:Biomarkers; D003037:Cobalt Radioisotopes; D016207:Cytokines