Characterization of a murine tail model for radiation-induced skin injury following localized irradiation at graded doses

PURPOSE: Radiation-induced skin injury (RISI) is common in both radiation therapy and accidental exposure. An appropriate animal model of RISI is of great significance for understanding its injury mechanism and developing medical countermeasures (MCMs). A reproducible, dose-dependent murine model of RISI was established via localized irradiation of the tail skin with graded doses. MATERIALS AND METHODS: C57BL/6 mice were employed to establish RISI model by irradiating 2 cm section of the mouse tail with 20 Gy, 30 Gy, and 40 Gy of single irradiation with RS2000 Biological Irradiator. Skin injuries were scored with a modified semi-quantitative scale based on Kumar scale. H&E staining, measurement of the thickness of epidermis and dermis, IHC for dopachrome tautomerase (DTC), IF staining for α-smooth muscle actin (α-SMA) and Masson staining were used for histopathological evaluations of RISI. RESULTS: A murine model of RISI was established via graded-dose X-ray irradiation of the tail, followed by comprehensive characterization and evaluation of its phenotypic traits. Dynamic alterations in cutaneous melanin-excessive early deposition and subsequent reduction-triggered by tail irradiation rendered radiation-induced erythema undetectable. To address this issue, we specifically revised the early damage scoring criteria of the RISI scale based on Kumar scale. As radiation dose increased, mice exhibited typical symptoms in the irradiated area, including dry desquamation (20 Gy), moist desquamation (30 Gy), ulcers and necrosis (40 Gy), which mimic the key features of clinical RISI. Further histopathological assessment demonstrated a strong correlation between the scoring system and histological changes. Concurrently, we discovered that in the later stage of this model, the interstitial tissue at irradiated site presented a fibrotic phenotype with good dose dependence. CONCLUSION: In conclusion, this study established an easily operable and highly reproducible tail irradiation model, providing one new platform for in-depth research on the mechanisms and translational applications of RISI.