The aim of this study was to analyze the variations of the main mediators of the four cytokine and growth factor families involved in inter-cellular exchanges during radiation-induced tissue degeneration in skin and muscles. An animal model of radiation-induced tissue degeneration was used for this purpose. The expression of proinflammatory, profibrotic, proangiogenic and stem cell mobilizing cytokines was analyzed using Western blot and the Bio-PlexH protein array technology. Additional histology and immnunochemistry studies were performed. Radiotherapy-induced late normal tissue injury within the irradiated field is a significant cause of morbidity and decrease quality of life in cancer patients. This justifies the evaluation of biomarkers predictive of late toxicity of radiation. The present study was performed in a model of late tissue radio-induced degeneration, enabling the assessment of histological changes and dysregulation of molecular mediators in irradiated tissues. Despite monodose irradiation, the histological and macroscopic modifications observed in this study were very similar to those observed after radiotherapy in humans. In our model, inflammation was maximal at 30 days, followed by fibrosis starting at 6 weeks, stabilizing at 3 months but sometimes continuing through successive stages. However, the main problem with the histological analysis of irradiated tissues is that radiation-induced injuries are focal so that analysis might miss some aspects of radiation-induced degeneration. Intra-and inter-observers reliabilities were good, but it clearly PCI-32765 appeared to us that histological analysis was not sufficient for precisely evaluating radio-induced tissular degeneration. In this context, the analysis of cytokine and mediator expression appeared to be an attractive method of evaluation of tissular changes after irradiation. Very often, the analysis of expression of cytokines and growth factors is based on immunochemistry or mRNA expression analyses. This gives an insight into the production of proteins, but without quantifying their real concentration in the tissue, which is determinant for the actions of the mediators studied. In this study, the methodology was based on the direct analysis of protein using the Bio-PlexH cytokine array. Indeed, the determined levels of expression of the key mediators in this study were coherent, and the expected correlations between pro- and anti-inflammatory mediators could be identified. This confirms the reliability of the methodology. Expression levels of the key mediators studied were consistent with the current model of radio-induced tissular degeneration. Similarly to other works, particularly in the skin, a high level of TGF-b1 was found throughout the study. TGF-b1 is known to control the regulation and inhibition of cell growth and the homeostasis of the extracellular matrix. Dysregulation of TGFb1 is involved in the development of fibroproliferative diseases. The increased expression of TGF-b1 was already present 6 weeks after irradiation, so that the initiation of this process was certainly earlier. Indeed, several authors found an induction of TGF-b1 during the first 24 hours after irradiation. In this study, a significant relation was found between TGF-b1 expression and histological scoring.