Abstract
The finding of new diagnostic and prognostic markers of local radiation injury, and particularly of the cutaneous radiation syndrome, is crucial for its medical management, in the case of both accidental exposure and radiotherapy side effects. Especially, a fast high-throughput method is still needed for triage of people accidentally exposed to ionizing radiation. In this study, we investigated the impact of localized irradiation of the skin on the early alteration of the serum proteome of mice in an effort to discover markers associated with the exposure and severity of impending damage. Using two different large-scale quantitative proteomic approaches, 2D-DIGE-MS and SELDI-TOF-MS, we performed global analyses of serum proteins collected in the clinical latency phase (days 3 and 7) from non-irradiated and locally irradiated mice exposed to high doses of 20, 40 and 80 Gy which will develop respectively erythema, moist desquamation and necrosis. Unsupervised and supervised multivariate statistical analyses (principal component analysis, partial-least square discriminant analysis and Random Forest analysis) using 2D-DIGE quantitative protein data allowed us to discriminate early between non-irradiated and irradiated animals, and between uninjured/slightly injured animals and animals that will develop severe lesions. On the other hand, despite a high number of animal replicates, PLS-DA and Random Forest analyses of SELDI-TOF-MS data failed to reveal sets of MS peaks able to discriminate between the different groups of animals. Our results show that, unlike SELDI-TOF-MS, the 2D-DIGE approach remains a powerful and promising method for the discovery of sets of proteins that could be used for the development of clinical tests for triage and the prognosis of the severity of radiation-induced skin lesions. We propose a list of 15 proteins which constitutes a set of candidate proteins for triage and prognosis of skin lesion outcomes.
Highlights
Damage to the skin induced by ionizing radiation is complex and leads to a defined range of specific reactions that frequently turn into a pathophysiological process: the cutaneous radiation syndrome (CRS) [1,2,3]
Using two-dimensional differential in-gel electrophoresis (2D-DIGE) coupled with mass spectrometry, we showed that serum proteome content is deeply altered from one day to one month following exposure of the skin to a high dose of ionizing radiation [18]
We investigated the power of proteomics to discriminate between non-irradiated and locally irradiated individuals, or between locally irradiated individuals that will develop lesion of different grades of severity
Summary
Damage to the skin induced by ionizing radiation is complex and leads to a defined range of specific reactions that frequently turn into a pathophysiological process: the cutaneous radiation syndrome (CRS) [1,2,3]. The dose received can be estimated by advanced techniques focused on different cytogenetic, genetic, physical and immunohistochemical parameters [7] These techniques are more suitable for whole- and partial-body irradiation than for local radiation exposure, require considerable expertise and are generally time-consuming. Following a radioactive source accident, the victim can be severely exposed locally but it is currently impossible to predict the outcome of the cutaneous lesion (i.e., necrosis or not). SELDI-TOF-MS, the 2D-DIGE approach remains a powerful method for the discovery of sets of proteins that could be used for the development of clinical tests for triage and the prediction of radiation-induced skin lesion severities
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
