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Although SNVs are also generated, the specific SNV patterns responsible for γ-ray mutagenesis remain unclear. Here, single base substitution (SBS) 17a, 17b, and 40 signatures are shown to arise mainly through SNV induction in A-T base pairs. Reactive oxygen species (ROS) are induced after 1–8 Gy, linking ROS to SBS17a/17b. Importantly, ROS-associated SNVs increase independently of SVs.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/single-base-substitution-signatures-17a-17b-and-40-are-induced-by-ray-irradiation-in-association-with-increased-reactive-oxidative-species/330332/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/single-base-substitution-signatures-17a-17b-and-40-are-induced-by-ray-irradiation-in-association-with-increased-reactive-oxidative-species/330332.png","ImageObject",300,407,{"name":92,"@type":93},"Lucas Martin","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Which single base substitution (SBS) signatures are induced by γ-ray irradiation?","Question",{"text":112,"@type":113},"γ-ray irradiation induces SBS17a, SBS17b, and SBS40 signatures.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do ROS relate to the induction of SBS17a and SBS17b?",{"text":117,"@type":113},"ROS are induced after γ-ray irradiation (1–8 Gy), and the results support ROS as a probable cause of SBS17a and SBS17b induction.",{"name":119,"@type":110,"acceptedAnswer":120},"Are ROS-associated SNVs linked to structural variants (SVs)?",{"text":121,"@type":113},"ROS-associated SNVs are induced independently of SVs, and the associated signatures are not observed alongside SV-associated patterns in the described way.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},330332,1790355914,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":46,"preview_page_count":4},8796095360427,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Heliyon 10 (2024) e28044  \nContents lists available at ScienceDirect  \nHeliyon  \njournal [homepage:](homepage: www.cell.com/heliyon)[ www.cell.com/heliyon](homepage: www.cell.com/heliyon)  \n| Research article\u003Cbr>Single base substitution signatures 17a, 17b, and 40 are induced by γ-ray irradiation in association with increased reactive oxidative species\u003Cbr>Yuya Manaka a, b, 1, Rika Kusumoto-Matsuo a, 1, Yusuke Matsunoa, Haruka Asaia, b, Ken-ichi Yoshiokaa, *\u003Cbr>a Laboratory of Genome Stability Maintenance, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan\u003Cbr>b Department of NCC Cancer Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima, Bunkyou-ku, Tokyo, Japan |\n| --- |\n| A B S T R A C T |\n| γ-Ray irradiation induces DNA double strand breaks (DSBs) and increases the risk of cancerization. Irradiated cells usually repair DSBs directly, but accumulate replication stress-associated DSBs, increasing the risk of structural variants (SVs). Although single nucleotide variants (SNVs) are also induced, it is still unclear which SNVs are induced by γ-ray irradiation. Here, we show that single base substitution (SBS) 17a, 17b, and 40 signatures were induced by γ-ray irradiation, which is mainly SNV induction in A-T bps. While SNVs induced by genomic instability were usually associated with SVs, SNVs induced by γ-ray irradiation and the associated signatures were not. As reactive oxygen species (ROS) are a possible cause of SBS17a and 17b, ROS were induced upon γ-ray irradiation (1–8 Gy), indicating the association of ROS for the SNV induction. Thus, our results reveal that ROS-associated SNVs are increased by irradiation, and that ROS-associated SNVs are induced independently of SVs. |\n\n1. Introduction  \nExposure to γ-ray irradiation is associated with cancerization [1–3]. It is generally believed that this is due to the DNA damage induced by irradiation. However, γ-ray irradiation induces many different types of DNA damage, such as DSBs, single strand breaks, and oxidative nucleotide adducts [4–6]. Presently, it is still unclear which type of damage is associated with cancerization and how this damage leads to mutations in cancer-driver genes. A recent study revealed that mouse embryonic fibroblast cells (MEFs) repair DSBs immediately after irradiation but subsequently accumulate replication stress-associated DSBs, thereby increasing the risk of genomic instability [7,8]. The resulting genomic instability can further increase the clonal evolution of cells mutated in the ARF/p53 pathway. These results suggest that accumulation of replication stress-associated DSBs is a primary risk factor for radiation-induced mutations. SVs and SNVs are widely induced in association with genomic instability. SVs including chromosomal translocations are induced by erroneous DSB repair between unpaired chromosomal ends, whereas SNVs are induced by DNA polymerase errors during DNA replication [9]. Although SVs and SNVs are induced by distinct pathways, their inductions are tightly associated with genomic instability, which can lead to clonal evolution of aberrant clones, as shown in the MEF model [10–12]. Even in the human genome, while SNVs in normal organs generally increase with age [13–15] as a consequence of DNA replication errors [16,17], those in the cancer genome are more tightly associated with SVs [10], implying that SNVs in cancer cells are often induced in association with  \n* Corresponding author.  \nE-mail address: [kyoshiok@ncc.go.jp](kyoshiok@ncc.go.jp) (K.-i. Yoshioka).  \n1 These authors equally contributed to this work.  \n[https://doi.org/10.1016/j.heliyon.2024.e28044](https://doi.org/10.1016/j.heliyon.2024.e28044)  \nReceived 26 October 2023; Received in revised form 3 March 2024; Accepted 11 March 2024 Available online 15 March 2024  \n2405-8440/© 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ([http://creativecomm","cbCaiac8Xu33tiYh","https://ap.wps.com/l/cbCaiac8Xu33tiYh","pdf",5316593,"English","# A B S T R A C T\n# 1. Introduction\n# 2. Materials and Methods\n## 2.1. Analyses of SVs and SNVs","[{\"question\":\"Which single base substitution (SBS) signatures are induced by γ-ray irradiation?\",\"answer\":\"γ-ray irradiation induces SBS17a, SBS17b, and SBS40 signatures.\"},{\"question\":\"How do ROS relate to the induction of SBS17a and SBS17b?\",\"answer\":\"ROS are induced after γ-ray irradiation (1–8 Gy), and the results support ROS as a probable cause of SBS17a and SBS17b induction.\"},{\"question\":\"Are ROS-associated SNVs linked to structural variants (SVs)?\",\"answer\":\"ROS-associated SNVs are induced independently of SVs, and the associated signatures are not observed alongside SV-associated patterns in the described way.\"}]","Single base substitution signatures 17a, 17b, and 40 are induced by γ-ray irradiation in association with increased reactive oxidative species | PDF",1789988205]