The preventive and protective effects of aspirin on radiation-induced skin injury
Radiation-induced skin injury (RISI) is a frequent complication of radiotherapy that can severely hinder treatment and endanger patients’ lives. Current treatments offer limited efficacy in reducing symptoms. This study explores the protective effect of aspirin (ASP) on RISI and its underlying mechanisms. As in vivo RISI models, 8 – 12-week-old C57BL/6 mice were irradiated with a single dose of 20 Gy X-rays to the skin of the right thigh, with sham-irradiated mice serving as controls. ASP was administered orally for 7 days before irradiation. Skin samples were collected on day 14 post-irradiation for single-cell RNA sequencing (sc-RNAseq). RISI severity was assessed daily using a modified RTOG/EORTC scoring system (scores ranging from 1 to 5.5). Our results showed that ASP delayed the onset of RISI and reduced its severity. The sc-RNAseq revealed an increased number of interfollicular epidermal cycling (IFE C) cells in irradiated skin, with some cells showing G2M cell cycle arrest. These IFE C cells exhibited elevated expression of stemness markers, indicating their importance in both RISI damage and subsequent repair. The ASP-treated group showed delayed skin injury onset and reduced peak severity compared to untreated controls. Furthermore, ASP appeared to promote homologous recombination repair of radiation-induced DNA damage, contributing to its protective effect. In conclusion, IFE C cells undergo G2M arrest to repair radiation-induced damage. ASP shows potential in preventing RISI, possibly through enhancing DNA repair. These findings suggest a novel therapeutic role for ASP in mitigating RISI.
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