Multiple blood-proteins approach for early-response exposure assessment using an in vivo murine radiation model.
OBJECTIVE
The aim was to evaluate the utility of multiple blood-protein biomarkers for early-response assessment of radiation exposure using a murine radiation model system.


METHODS
BALB/c male mice (8-10 weeks old) were exposed to whole-body 60Co gamma-rays (10 cGy min(-1)) over a broad dose range (0-7 Gy). Blood protein biomarkers (i.e., Growth Arrest and DNA Damage Inducible Gene 45 or GADD45alpha, interleukin 6 or IL-6, and serum amyloid A or SAA) were measured by enzyme linked immunosorbent assay (ELISA) at 4, 24, 48, and 72 h after total-body irradiation (TBI).


RESULTS
Time- and dose-dependent increases in the protein targets were observed. The use of multiple protein targets was evaluated using multiple linear regression analysis to provide dose-response calibration curves for dose assessment. Multivariate discriminant analysis demonstrated enhanced dose-dependent separation of irradiated animals from control as the number of biomarkers increased.


CONCLUSIONS
Results from this study represent a proof-of-concept for multiple blood-proteins biodosimetry approach. It was demonstrated for the first time that protein expression profile could be developed not only to assess radiation exposure in male BALB/c mice but also to distinguish the level of radiation exposure, ranging from 1-7 Gy.
Uniformed Services University, Armed Forces Radiobiology Research Institute, Scientific Research Department, Bethesda, Maryland 20889-5603, USA. ossetrova@afrri.usuhs.mil
Natalia I
NI
Ossetrova
William F
WF
Blakely
D054508:Acute Radiation Syndrome / Q000097:blood / Q000175:diagnosis; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000097:blood; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000097:blood; D011833:Radiation Injuries, Experimental / Q000097:blood*; D018788:Radioactive Hazard Release; D018570:Risk Assessment; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014916:Whole-Body Irradiation / Q000009:adverse effects; D000097642:GADD45 Proteins
D015415:Biomarkers; D001798:Blood Proteins; D018797:Cell Cycle Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D000685:Serum Amyloid A Protein; C499072:Gadd45a protein, mouse; D000097642:GADD45 Proteins