The urine proteome as a biomarker of radiation injury

Terrorist attacks or nuclear accidents could expose large numbers of people to ionizing radiation, and early biomarkers of radiation injury would be critical for triage, treatment, and follow-up of such individuals. However, no such biomarkers have yet been proven to exist. We tested the potential of high throughput proteomics to identify protein biomarkers of radiation injury after total body X-ray irradiation (TBI) in a rat model. Subtle functional changes in the kidney are suggested by increased glomerular permeability for macromolecules measured within 24 h after TBI. Ultrastructural changes in glomerular podocytes included partial loss of the interdigitating organization of foot processes. Analysis of urine by LC-MS/MS and 2-DE showed significant changes in the urine proteome within 24 h after TBI. Tissue kallikrein 1-related peptidase, cysteine proteinase inhibitor cystatin C and oxidized histidine were found to be increased while a number of proteinase inhibitors including kallikrein-binding protein and albumin were found to be decreased postirradiation. Thus, TBI causes immediately detectable changes in renal structure and function and in the urinary protein profile. This suggests that both systemic and renal changes are induced by radiation and it may be possible to identify a set of biomarkers unique to radiation injury.