{"title":"Comparative Transcriptomic Analysis Unveils Divergent Effects of FLASH Versus Conventional Irradiation on Skin Cells.","authors":"Mengmeng Xu, Qiliang Peng, Jun Zhang, Zhiming Xu, Xinyang Cheng, Zhifei Cao, Yongsheng Zhang","doi":"10.1177/15593258251342837","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>FLASH radiotherapy is garnering attention for its capacity to diminish skin toxicity without compromising tumoricidal efficacy, presenting a stark contrast to conventional (CONV) radiotherapy. Despite its promise, the underlying molecular mechanisms of FLASH irradiation (FLASH-IR) on skin are not yet fully elucidated.</p><p><strong>Methods: </strong>This study investigated the transcriptomic responses of human foreskin fibroblast cells (HFF-1) via the FLASH-IR or CONV irradiation (CONV-IR), employing the next-generation RNA sequencing (RNA-seq) to capture the gene expression profiles. Our comparative analysis aimed to dissect the cellular and molecular pathways influenced by these two irradiation methods.</p><p><strong>Results: </strong>We identified a spectrum of differentially expressed genes (DEGs), signaling pathways, and transcriptional networks that were either shared or divergent between FLASH-IR and CONV-IR. Particularly, transcription factor NR4A1 showed significant upregulation in response to FLASH-IR, while chromatin stability factor ELF3 was markedly downregulated following CONV-IR. The top 10 up-regulated DEGs were subjected to qPCR validation, confirming their differential expression in response to FLASH-IR and CONV-IR.</p><p><strong>Conclusion: </strong>Collectively, our findings delineate unique regulatory landscapes of FLASH-IR and CONV-IR on skin cells, corroborating established effects and shedding new light on the molecular interplay within the context of ultra-high dose radiation.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"23 2","pages":"15593258251342837"},"PeriodicalIF":2.3000,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092997/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Dose-Response","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/15593258251342837","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: FLASH radiotherapy is garnering attention for its capacity to diminish skin toxicity without compromising tumoricidal efficacy, presenting a stark contrast to conventional (CONV) radiotherapy. Despite its promise, the underlying molecular mechanisms of FLASH irradiation (FLASH-IR) on skin are not yet fully elucidated.
Methods: This study investigated the transcriptomic responses of human foreskin fibroblast cells (HFF-1) via the FLASH-IR or CONV irradiation (CONV-IR), employing the next-generation RNA sequencing (RNA-seq) to capture the gene expression profiles. Our comparative analysis aimed to dissect the cellular and molecular pathways influenced by these two irradiation methods.
Results: We identified a spectrum of differentially expressed genes (DEGs), signaling pathways, and transcriptional networks that were either shared or divergent between FLASH-IR and CONV-IR. Particularly, transcription factor NR4A1 showed significant upregulation in response to FLASH-IR, while chromatin stability factor ELF3 was markedly downregulated following CONV-IR. The top 10 up-regulated DEGs were subjected to qPCR validation, confirming their differential expression in response to FLASH-IR and CONV-IR.
Conclusion: Collectively, our findings delineate unique regulatory landscapes of FLASH-IR and CONV-IR on skin cells, corroborating established effects and shedding new light on the molecular interplay within the context of ultra-high dose radiation.
Dose-ResponsePHARMACOLOGY & PHARMACY-RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
CiteScore
4.90
自引率
4.00%
发文量
140
审稿时长
>12 weeks
期刊介绍:
Dose-Response is an open access peer-reviewed online journal publishing original findings and commentaries on the occurrence of dose-response relationships across a broad range of disciplines. Particular interest focuses on experimental evidence providing mechanistic understanding of nonlinear dose-response relationships.