The preventive and protective effects of aspirin on radiation-induced skin injury

Zhaoming Zhou , Yong Feng , Wei Qiao

Advances in Radiotherapy & Nuclear Medicine ›› 2025, Vol. 3 ›› Issue (1) : 57 -70.

PDF (3704KB)
Advances in Radiotherapy & Nuclear Medicine ›› 2025, Vol. 3 ›› Issue (1) : 57 -70. DOI: 10.36922/arnm.5829
ORIGINAL RESEARCH ARTICLES
research-article

The preventive and protective effects of aspirin on radiation-induced skin injury

Author information +
History +
PDF (3704KB)

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 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.

Keywords

Radiation-induced skin injury / Single-cell RNA sequencing / Interfollicular epidermal cells / Aspirin / G2/M cell cycle arrest / DNA repair

Cite this article

Download citation ▾
Zhaoming Zhou, Yong Feng, Wei Qiao. The preventive and protective effects of aspirin on radiation-induced skin injury. Advances in Radiotherapy & Nuclear Medicine, 2025, 3(1): 57-70 DOI:10.36922/arnm.5829

登录浏览全文

4963

注册一个新账户 忘记密码

Acknowledgments

None.

Funding

None.

Conflict of interest

The authors declare they have no competing interests.

Author contributions

Conceptualization: Zhaoming Zhou, Wei Qiao

Data curation: All authors

Formal analysis: Yong Feng

Funding acquisition: Wei Qiao

Investigation: Zhaoming Zhou

Methodology: Zhaoming Zhou

Project administration: Yong Feng

Resources: Wei Qiao

Software: Zhaoming Zhou

Supervision: Wei Qiao

Validation: Zhaoming Zhou

Visualization: Zhaoming Zhou

Writing - original draft: Zhaoming Zhou

Writing - review & editing: All authors

Ethics approval and consent to participate

This study did not include human participants, human data, or human tissue. The animal experiments were carried out in accordance with ethical procedures and the protocols were approved by the Ethics Committee for Laboratory Animals of the Southern Medical University (L2019074).

Consent for publication

Not applicable.

Availability of data

The data used in this study will be available from the corresponding author upon reasonable request.

References

[1]

Wei J, Meng L, Hou X, et al. Radiation-induced skin reactions: Mechanism and treatment. Cancer Manag Res. 2018; 11:167-177. doi: 10.2147/CMAR.S188655

[2]

Brown KR, Rzucidlo E. Acute and chronic radiation injury J Vasc Surg. 2011; 53(15):15S-21S. doi: 10.1016/j.jvs.2010.06.175

[3]

Wang Y, Tu W, Tang Y, Zhang S. Prevention and treatment for radiation-induced skin injury during radiotherapy. Radiat Med Prot. 2020; 1(2):60-68. doi: 10.1016/j.radmp.2020.02.004

[4]

Kim JH, Kolozsvary AJJ, Jenrow KA, Brown SL. Mechanisms of radiation-induced skin injury and implications for future clinical trials. Int J Radiat Biol. 2013;89:311-318. doi: 10.3109/09553002.2013.765055

[5]

Jiang H, Swacha P, Aung KM, Gekara NO. Aspirin protects against genotoxicity by promoting genome repair. Cell Res. 2023; 33(4):325-327. doi: 10.1038/s41422-023-00783-6

[6]

Laube M, Kniess T, Pietzsch J. Development of antioxidant COX-2 inhibitors as radioprotective agents for radiation therapy-A hypothesis-driven review. Antioxidants (Basel). 2016; 5(2):14. doi: 10.3390/antiox5020014

[7]

Li X, Heyer WD. Homologous recombination in DNA repair and DNA damage tolerance. Cell Res. 2008; 18(1):99-113. doi: 10.1038/cr.2008.1

[8]

Kim KY, Seol JY, Jeon GA, Nam MJ. The combined treatment of aspirin and radiation induces apoptosis by the regulation of bcl-2 and caspase-3 in human cervical cancer cell. Cancer Lett. 2003; 189(2):157-166. doi: 10.1016/S0304-3835(02)00519-0

[9]

Curras-Alonso S, Soulier J, Defard T, et al. An interactive murine single-cell atlas of the lung responses to radiation injury. Nat Commun. 2023; 14(1):2445. doi: 10.1038/s41467-023-38134-z

[10]

Hoeller U, Tribius S, Kuhlmey A, Grader K, Fehlauer F, Alberti W. Increasing the rate of late toxicity by changing the score? A comparison of RTOG/EORTC and LENT/SOMA scores. Int J Radiat Oncol Biol Phys. 2003; 55(4):1013-1018. doi: 10.1016/S0360-3016(02)04202-5

[11]

Gribov A, Sill M, Lück S, et al. SEURAT: Visual analytics for the integrated analysis of microarray data. BMC Med Genomics. 2010; 3(1):21. doi: 10.1186/1755-8794-3-21

[12]

Yu G, Wang LG, Han Y, He QY. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-287. doi: 10.1089/omi.2011.0118

[13]

Reimand J, Isserlin R, Voisin V, et al. Pathway enrichment analysis and visualization of omics data using g: Profiler, GSEA, Cytoscape and EnrichmentMap. Nat Protoc. 2019; 14(2):482-517. doi: 10.1038/s41596-018-0103-9

[14]

Nguyen QH, Pervolarakis N, Blake K, et al. Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity. Nat Commun. 2018;9:2028. doi: 10.1038/s41467-018-04334-1

[15]

Vorstandlechner V, Laggner M, Kalinina P, et al. Deciphering the functional heterogeneity of skin fibroblasts using singlecell RNA sequencing. FASEB J. 2020; 34(3):3677-3692. doi: 10.1096/fj.201902001RR

[16]

Szabo PA, Levitin HM, Miron M, et al. Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease. Nat Commun. 2019; 10(1):4706. doi: 10.1038/s41467-019-12464-3

[17]

Paldor M, Levkovitch-Siany O, Eidelshtein D, et al. Singlecell transcriptomics reveals a senescence‐associated IL‐6/ CCR6 axis driving radiodermatitis. EMBO Mol Med. 2022; 14(8):e15653. doi: 10.15252/emmm.202115653

[18]

Lehmann GL, Hanke-Gogokhia C, Hu Y, et al. Singlecell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid. J Exp Med. 2020; 217(6):e20190730. doi: 10.1084/jem.20190730

[19]

Joost S, Annusver K, Jacob T, et al. The molecular anatomy of mouse skin during hair growth and rest. Cell Stem Cell. 2020; 26(3):441-457.e7. doi: 10.1016/j.stem.2020.01.012

[20]

Morse M, Lennon N, Livak K. Monocle: Cell Counting, Differential Expression, and Trajectory Analysis for Singlecell RNA-Seq Experiments; 2016. Available from: https:// www.semanticscholar.org/paper/monocle-%3a-cellcounting-% 2c-differential-expression-%2c-morse-lennon/ c7147e72a6ff07dacf7e72d9e2664d87d00f5b29 [Last Accessed on 2024 Nov 08].

[21]

Joost S, Zeisel A, Jacob T, et al. Single-cell transcriptomics reveals that differentiation and spatial signatures shape epidermal and hair follicle heterogeneity. Cell Syst. 2016; 3(3):221-237.e9. doi: 10.1016/j.cels.2016.08.010

[22]

Cuzick J, Otto F, Baron JA, et al. Aspirin and nonsteroidal anti-inflammatory drugs for cancer prevention: An international consensus statement. Lancet Oncol. 2009; 10(5):501-507. doi: 10.1016/S1470-2045(09)70035-X

[23]

Sisakht M, Darabian M, Mahmoodzadeh A, et al. The role of radiation induced oxidative stress as a regulator of radioadaptive responses. Int J Radiat Biol. 2020; 96(5):561-576. doi: 10.1080/09553002.2020.1721597

[24]

Dong Z, Yang L, Jiao J, et al. Aspirin in combination with gastrodin protects cardiac function and mitigates gastric mucosal injury in response to myocardial ischemia/ reperfusion. Front Pharmacol. 2022;13:995102. doi: 10.3389/fphar.2022.995102

[25]

Zhao B, Rothenberg E, Ramsden DA, Lieber MR. The molecular basis and disease relevance of non-homologous DNA end joining. Nat Rev Mol Cell Biol. 2020; 21(12):765-781. doi: 10.1038/s41580-020-00297-8

[26]

Ensminger M, L.brich M. One end to rule them all: Non-homologous end-joining and homologous recombination at DNA double-strand breaks. Br J Radiol. 2020; 93(1115):20191054. doi: 10.1259/bjr.20191054

[27]

Alfonso L, Ai G, Spitale RC, Bhat GJ. Molecular targets of aspirin and cancer prevention. Br J Cancer. 2014; 111(1):61-67. doi: 10.1038/bjc.2014.271

[28]

Salehifar E, Hosseinimehr SJ, Thorat MA, Cuzick J. The use of cyclooxygenase-2 inhibitors for improvement of efficacy of radiotherapy in cancers. Drug Discov Today. 2016; 21(4):654-662. doi: 10.1016/j.drudis.2016.02.019

[29]

Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol. 2012; 9:259-267. doi: 10.1038/nrclinonc.2011.199

[30]

Thorat MA, Cuzick J. Role of aspirin in cancer prevention. Curr Oncol Rep. 2013; 15(6):533-540. doi: 10.1007/s11912-013-0351-3

AI Summary AI Mindmap
PDF (3704KB)

181

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/