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

## TL;DR

This study created a mouse model to study early and late skin reactions caused by radiation therapy in cancer patients.

## Contribution

A novel murine model was developed to replicate both early and late radiation-induced skin reactions for future research.

## Key findings

- The 30 Gy group showed grade 2 early reactions resolving by day 30, while the 50 Gy group showed grade 3 reactions resolving by day 35.
- Early 50 Gy reactions included dermal inflammation and hair follicle loss, while late effects included collagen buildup and persistent hair loss.
- The model effectively mimics clinical and histological features of radiation-induced skin reactions.

## Abstract

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.

The online version contains supplementary material available at 10.1038/s41598-026-39414-6.