MALDI and LCMS Identifications of Early Protein and LA-ICP-MS Identification of Early Metal Biomarkers of Ionizing Radiation

MALDI and LCMS Identifications of Early Protein and LA-ICP-MS Identification of Early Metal Biomarkers of Ionizing Radiation

Abstract:
The goal of this project was identification of early protein biomarkers of total body ionizing radiation (TBI). Ionizing radiation (IR) experiments demonstrated radiation dose-related changes in exposed murine buccal mucosa and tongue tissue. Matrix assisted laser desorption ionization mass spectrometry (MALDI) imaging (IMS) co-registered with contiguous histopathologic sections demonstrated free tissue albumin and other proteins after 2 Gy TBI but not in control non-irradiated tissues. These findings were confirmed by MALDI and liquid chromatography mass spectrometry (LCMS) of protein extracts from irradiated tissue. Laser ablation ion coupled plasma mass spectrometry (LA-ICP-MS) measurements of Fe, Cu, and Zn demonstrated early changes as well, especially in the elevated levels of Zn in the first four days after 2 Gy, TBI, the threshold dose for radiation sickness. These results are proof of principle that there are protein, peptide, and elemental biomarkers of acute IR, and they could be used to identify victims of radiation exposure, specifically, the 2 Gy threshold dose for radiation sickness in a civilian or terrorist nuclear mass casualty.