Early Detection of Inflammatory Response and the Subsequent Health Outcomes Due to High LET Particle Radiation: An Integrated Metabolomics Study
EMSL Project ID
24695
Abstract
In a recent small scale study focusing on rat brain, we have found that NMR-detectable metabolites (e.g., the concentrations of alanine, acetate, glutamate, creatine, choline, phosphocholine, inositol and myo-inositol, etc.) are increased significantly when rats are exposed to whole body high linear energy transfer (high LET) iron ions at radiation doses as low as 16 cGy. We hypothesize that metabolite biomarkers sensitive to high energy particle radiation will be detectable and quantifiable in metabolomics-based studies using well established, and in part unique, high resolution and high sensitivity NMR and capillary LC-MS metabolomics methods in our laboratory. In addition, we propose that a low dose of high LET radiation causes a low grade inflammatory response and triggers a cascade of molecular events detectable with our approach. We will perform an integrated, sensitive NMR and LC-MS metabolomics study of the impact of exposing mice and rats to 0, 0.2, 0.5, 2 and 3Gy using both high LET proton and iron ions particle radiation. The metabolic perturbations in the animal's global physiology and the subsequent health outcomes will be investigated from two hours to 1 year post irradiation using key body fluids and excised tissues. In parallel we will also investigate the impact of exposing mice and rats to gamma-rays at the same dose and dose rate to address the differences in dose-rate effects between proton, iron ions and gamma-rays. We will elucidate the detailed molecular mechanisms of high LET radiation, with emphasis on understanding the molecular basis of radiation through the discovery of metabolic "signatures". This new knowledge will be translated to benefit human health in space exploration.
Project Details
Project type
Limited Scope
Start Date
2007-03-10
End Date
2007-04-26
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members