Establishing a robust preclinical model to investigate early and late radiation-induced skin reactions

Radiation-induced skin reactions (RISRs) adversely affect cancer patients by limiting treatment adherence and quality of life (QoL). The current study aimed to establish a murine model for early and late RISR by fractionated radiation, with 30 Gy (10 Gy X 3 sessions) and 50 Gy (10 Gy X 5 sessions) irradiation of the right hind limb of male Swiss albino mice. Early RISRs were monitored for 30 days via blinded RTOG grading, and tissue samples from days 15 and 30 were harvested for histological and morphometric analysis (H&E staining). For late RISR, mice exposed to 50 Gy were examined for 120 days by phenotypical, histological, and morphometric evaluations (H&E and Masson's trichrome staining). The 30 Gy group presented a median RTOG grade of 2, resolving by day 30, whereas the 50 Gy group presented a median grade of 3, resolving by day 35. Early RISR in the 50 Gy group revealed dermal inflammation, ulceration, cellular infiltration, and reduced hair follicle density, with late effects of dermal indentations, excessive collagen, cellular inflammation, and persistent hair follicle loss (p < 0.05). The present murine model effectively replicated early and late RISR clinical and histological features for mechanistic investigations and developing therapeutic strategies in future studies.