Gamma-Tocotrienol, A Radiation Countermeasure, Reverses Proteomic Changes In Serum Following Total-Body Gamma Irradiation In Mice

Radiological incidents or terrorist attacks would likely expose civilians and military personnel to high doses of ionizing radiation, leading to the development of acute radiation syndrome (ARS). While the effects and symptoms of high dose radiation exposure have been established, prophylactic treatments and methods for determining the extent of exposure remain limited. We examined the effectiveness of prophylactic administration of a developmental radiation countermeasure, g-tocotrienol (GT3), in a total-body irradiation (TBI) mouse model. CD2F1 mice received GT3 24 h prior to 11 Gy cobalt-60 gamma-irradiation, a supralethal dose for this strain. Two-dimensional differential in-gel electrophoresis was followed by mass spectrometry and Ingenuity Pathway Analysis (IPA). Analysis revealed a change in expression of 18 proteins in response to TBI, and these changes were reversed with prophylactic treatment of GT3. IPA revealed a network of associated proteins involved in cellular movement, immune cell trafficking, and inflammatory response. Of particular interest, significant expression changes in beta-2-glycoprotein 1, alpha-1-acid glycoprotein 1, alpha-2-macroglobulin, complement C3, mannose-binding protein C, and major urinary protein 6 were noted after TBI and reversed with GT3 treatment. This study reports the network and specific serum proteins which could be translated as biomarkers of both radiation injury and protection by radiation countermeasures.