Investigation of the serum proteome to look for ionizing radiation biomarkers
Congress title :SFEAP 2006
Congress town :Saint-Malo
Congress date :16/10/2006
Radiation-induced lesion outcomes of normal tissues are difficult to predict. In particular, radiotherapy or local exposure to a radioactive source by accident can trigger strong injury to the skin. The finding of prognostic biomarkers is of fundamental relevance for the prediction of lesion apparition and its evolution, and for the settlement of therapeutic strategies. In order to study radiation-induced cutaneous lesions, we developed a mouse model in which the dorsal skin was selectively exposed to ionizing radiation. Two-dimensional difference gel electrophoresis (2-D DIGE) coupled with mass spectrometry were used to investigate proteins altered in expression and/or post-translational modification in serum. Proteome changes were monitored from one day to one month post-irradiation at 40 Gy in this specific model developing reproducible clinical symptoms ranging from erythema to skin ulceration followed by wound healing. About 50 proteins (including some isoforms and likely post-translational variants), representing 20 different proteins, that exhibited significant kinetic expression changes were identified using mass spectrometry and database interrogation. Several proteins were from day one down- or up-regulated and could turn out to be good candidates to prognosticate the evolution of skin lesion. In addition, we observed shifts in isoelectric point (pI) of several spot trains, revealing potential post-translational modification changes which could also serve as indicators of irradiation. On the other hand, we report the first serum proteome analysis of a man strongly and locally exposed to ionizing radiation by accident. 2-D DIGE analysis of his serum compared to serums from healthy donors revealed many changes in expression level and likely in post-translational modification. Identifications of variant proteins using mass spectrometry will be presented and discussed. In conclusion, our results clearly indicate that serum protein content is dynamically modified after a local irradiation of the skin, showing that investigation of the serum proteome could be of great importance to find out diagnostic or prognostic indicators.