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Advances in Radiotherapy &

                                                                            Nuclear Medicine




                                        ORIGINAL RESEARCH ARTICLE
                                        The preventive and protective effects of aspirin

                                        on radiation-induced skin injury



                                                                                 3
                                                                   1
                                        Zhaoming Zhou 1,2  , Yong Feng *, and Wei Qiao *
                                        1 Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer
                                        Research and the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
                                        2 Department of Radiation Medicine, Guangdong Provincial Key Laboratory of  Tropical Disease
                                        Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
                                        3 Department of Radiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research and The
                                        Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China




                                        Abstract
                                        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
            *Corresponding authors:
            Yong Feng                   was assessed daily using a modified RTOG/EORTC scoring system (scores ranging
            (fengyong@njmu.edu.cn)      from 1 to 5.5). Our results showed that ASP delayed the onset of RISI and reduced its
            Wei Qiao                    severity. The sc-RNAseq revealed an increased number of interfollicular epidermal
            (13914707452@njmu.edu.cn)
                                        cycling (IFE C) cells in irradiated skin, with some cells showing G2M cell cycle arrest.
            Citation: Zhou Z, Feng Y, Qiao W.   These IFE C cells exhibited elevated expression of stemness markers, indicating their
            The preventive and protective
            effects of aspirin on radiation-  importance in both RISI damage and subsequent repair.  The ASP-treated group
            induced skin injury. Adv Radiother   showed delayed skin injury onset and reduced peak severity compared to untreated
            Nucl Med. 2025;3(1):57-70.   controls. Furthermore, ASP  appeared to  promote homologous  recombination
            doi: 10.36922/arnm.5829     repair of radiation-induced DNA damage, contributing to its protective effect. In
            Received: November 9, 2024  conclusion, IFE C cells undergo G2M arrest to repair radiation-induced damage. ASP
            Revised: December 9, 2024   shows potential in preventing RISI, possibly through enhancing DNA repair. These
                                        findings suggest a novel therapeutic role for ASP in mitigating RISI.
            Accepted: January 3, 2025
            Published online: January 27,
            2025                        Keywords: Radiation-induced skin injury; Single-cell RNA sequencing; Interfollicular
                                        epidermal cells; Aspirin; G2/M cell cycle arrest; DNA repair
            Copyright: © 2025 Author(s).
            This is an Open-Access article
            distributed under the terms of the
            Creative Commons Attribution
            License, permitting distribution,   1. Introduction
            and reproduction in any medium,
            provided the original work is   Radiation-induced skin injury (RISI) is a common complication in patients undergoing
            properly cited.             radiotherapy, particularly in cancers that involve the skin or adjacent tissues. The
            Publisher’s Note: AccScience   severity of RISI can range from mild erythema to severe necrosis, posing a significant
            Publishing remains neutral with   risk to patient well-being and potentially necessitating interruptions in the course of
            regard to jurisdictional claims in
            published maps and institutional   radiotherapy. Such disruptions can compromise the effectiveness of cancer treatment,
                                                                        1,2
            affiliations                leading to poorer outcomes for patients . The clinical manifestations of RISI include

            Volume 3 Issue 1 (2025)                         57                             doi: 10.36922/arnm.5829
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