Proteomic Analysis of Plasma at the Preterminal Stage of Rhesus Nonhuman Primates Exposed to a Lethal Total-Body Dose of Gamma-Radiation

Abstract

The identification and validation of radiation biomarkers is critical for assessing the radiation dose received in exposed individuals and for developing radiation medical countermeasures that can be used to treat acute radiation syndrome (ARS). Additionally, a fundamental understanding of the effects of radiation injury could further aid in the identification and development of therapeutic targets for mitigating radiation damage. In this study, blood samples were collected from fourteen male nonhuman primates (NHPs) that were exposed to 7.2 Gy ionizing radiation at various time points (seven days prior to irradiation; 1, 13, and 25 days post-irradiation; as well as immediately prior to the euthanasia of moribund animals (preterminal)). Plasma was isolated from these samples and was analyzed using a liquid chromatography tandem mass spectrometry approach in an effort to determine the effects of radiation on plasma proteomic profiles. Of particular interest was to determine if the expression of certain proteins reacted to radiation in a way that would act as a predictor for health decline leading to a preterminal phenotype. Our results suggest that radiation induced a diverse temporal pattern among protein expression that displayed prominent changes within NHP proteomic plasma profiles. Of these significantly altered proteins, several play important roles in certain biological processes such as hemostasis, inflammation, and immune response.