Multiple blood-proteins approach for early-response exposure assessment using an in vivo murine radiation model

Int J Radiat Biol. 2009;85(10):837-50.

Abstract

Purpose: 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.

Material and 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Radiation Syndrome / blood
  • Acute Radiation Syndrome / diagnosis
  • Animals
  • Biomarkers / blood
  • Blood Proteins / metabolism*
  • Cell Cycle Proteins / blood
  • Disease Models, Animal
  • Dose-Response Relationship, Radiation
  • Gamma Rays / adverse effects
  • Humans
  • Interleukin-6 / blood
  • Linear Models
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Multivariate Analysis
  • Nuclear Proteins / blood
  • Radiation Injuries, Experimental / blood*
  • Radioactive Hazard Release
  • Risk Assessment
  • Serum Amyloid A Protein / metabolism
  • Whole-Body Irradiation / adverse effects

Substances

  • Biomarkers
  • Blood Proteins
  • Cell Cycle Proteins
  • Gadd45a protein, mouse
  • Interleukin-6
  • Nuclear Proteins
  • Serum Amyloid A Protein