Longitudinal multimodal characterization of radiation dermatitis in a C57BL/6J mouse model

Summary: Radiation dermatitis (RD) is a common sequela of radiation therapy (RT), affecting over half of cancer patients. Its cutaneous manifestations—ranging from erythema and desquamation to ulceration and fibrosis—can hinder oncologic treatment completion. Despite its prevalence, RD's pathogenesis remains poorly understood. As such, we aim to develop a temporal murine model of RD using clinical grading, objective skin parameters, histopathology, and gene expression analysis of inflammatory markers. Ten-week-old female C57BL/6J mice were radiated with 35 Gy to the left flank. Mice (n=19) were split into five groups: sham (no RT), and four post-RT groups with weekly data collection for four weeks. Data included clinical grading, measurements for erythema, fibrosis, and transepidermal water loss (TEWL), biopsies, and serum samples. Blinded clinical images were graded from 1-4 and blinded histologic images with variables on a 1-5 scale. Expression of selected pro-inflammatory cytokines were assessed using RNA extraction and quantitative PCR. Clinical grading increased from zero at baseline to two by week four across all groups, mirroring progression of skin lesions. Objective probe measurements for erythema and fibrosis significantly increased over the four weeks, while TEWL peaked at week three. Certain histologic variables (epidermal ulceration and follicular loss) increased significantly over the four weeks, while others (dermal and hypodermal inflammation, dermal fibrosis, glandular loss, and total score) peaked at week one, decreased, then progressed through week four. Pro-inflammatory markers IL-17A and IL-1b were significantly upregulated at week four, while IL-6 peaked at week three. TGF-B1 showed an increasing trend but did not reach significance. Our murine model provides a clinical, histologic, and molecular framework for understanding RD progression over time. Additional studies are needed to further validate this model, potentially supporting future research on therapeutic interventions. Jasmine H. Wong¹, Sharen Rivas¹, Wade Koba¹, Chandan Guha¹, Adnan Mir¹, Beth N. McLellan¹, Kosaku Shinoda¹ 1. Montefiore Medical Center, New York, NY, United States. Translational Studies: Cell and Molecular Biology