Development of an easy-to-handle murine model for the characterization of radiation-induced gross and molecular changes in skin

ABSTRACT

BACKGROUND: Radiation-induced skin injury is a dose-limiting complication of radiotherapy. To investigate this problem and to develop a framework for making decisions on treatment and dose prescription, a murine model of radiation-induced skin injury was developed. METHODS: The dorsal skin of the mice was isolated, and irradiation was applied at single doses of 15, 30, and 50 Gy. The mice were followed for 12 weeks with serial photography and laser Doppler analysis. Sequential skin biopsy samples were obtained and subjected to a histological analysis, immunostaining against transforming growth factor beta (TGF-β), and Western blotting with Wnt-3 and β-catenin. Increases in the levels of TGF-β, Wnt, and β-catenin were detected after irradiation. RESULTS: All tested radiation doses caused progressive dermal thickening and fibrosis. The cause of this process, however, may not be radiation alone, as the natural course of wound healing may elicit a similar response. The latent appearance of molecular and histological markers that induce fibrosis in the 15 Gy group without causing apparent gross skin injuries indicates that 15 Gy is an appropriate dose for characterizing the effects of chronic irradiation alone. Thus, this model best mimics the patterns of injury that occur in human subjects. CONCLUSIONS: This animal model can be used to elucidate the gross and molecular changes that occur in radiation-induced skin injury and provides an effective platform for studying this adverse effect without complicating the process of wound healing.