P53-dependent bystander cell-killing effect in human cell lines irradiated with carbon ions

P53-dependent bystander cell-killing effect in human cell lines irradiated with carbon ions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article P53-dependent bystander cell-killing effect in human cell lines irradiated with carbon ions Masao Suzuki, Tomoo Funayama, Michiyo Suzuki, Hisashi Kitamura This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6953553/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Since 1994, Phase I/II clinical studies and cancer radiotherapy have used carbon-ion beams at the Heavy Ion Medical Accelerator in Chiba (HIMAC) of the National Institutes for Quantum Science and Technology (QST). Biological effects of direct irradiation for high linear energy transfer (LET) radiation are reported to be higher than those for low-LET X-rays or gamma rays. However, it remains unclear whether indirect biological effects in cells, such as bystander effects, can be described as the ability of cells affected by irradiation to convey manifestations of damage to neighboring cells that are not directly irradiated. In this study, we examined the P53-dependent bystander cell-killing effect in human cells irradiated with either a broad beam or a microbeam of carbon ions. Ten human cell lines of normal origin or cancerous origin with wild-type or mutated type P53-gene status were used in this study. The study results demonstrated an enhanced cell-killing effect by carbon ions—beyond what would be expected based solely on our specific irradiation protocols—in cells with wild-type P53, but not in cells with mutant P53, assuming no bystander effect. Furthermore, the results suggest that gap junction-mediated cell-to-cell communication plays an important role in inducing a bystander cell-killing effect in cells with wild-type P53. These results should be applied in clinical studies for developing heavy-ion radiotherapy to determine the mechanism(s) of the radiation-induced bystander cell-killing effect. bystander cell-killing effect heavy-ion microbeam gap-junction mediated cell-to-cell communication P53 gene Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6953553","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":476360889,"identity":"14f1c1ea-b70e-4bd5-886b-405c2fa6d049","order_by":0,"name":"Masao Suzuki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIiWNgGAWjYJACxgYDKOsDTEiCWC2MM2CKCWuBMph5CCtmYJCfkf5MckYBQzR//+GHj23K6uoY+BcfYLDcgVuLwY2ENMkNBgy5M26kGRvnnDsswSDxLIFB8gweLRIJxyQfALU03GAwk85tOwDUcsaAQbINn8MS28Ba5p8//k3asq2OsBaGG8lsYIdtOJBjJs3YxizBwN+DX4vBmWfMljMMJHI33sgpNuw5d1iyTYIt4QA+v8i3pz+82fPHJnfe+eMbH/woq+Pn5z988LEknhCDAlhssAGRRALDYckGglpgAKiFgf8AA+NH4rWMglEwCkbB8AcAJVdOFzfb8S0AAAAASUVORK5CYII=","orcid":"","institution":"National Institutes for Quantum Science and Technology (QST)","correspondingAuthor":true,"prefix":"","firstName":"Masao","middleName":"","lastName":"Suzuki","suffix":""},{"id":476360891,"identity":"856054b3-3a5a-4253-8f64-3a39cd549def","order_by":1,"name":"Tomoo Funayama","email":"","orcid":"","institution":"National Institutes for Quantum Science and Technology (QST)","correspondingAuthor":false,"prefix":"","firstName":"Tomoo","middleName":"","lastName":"Funayama","suffix":""},{"id":476360895,"identity":"7e546df2-a3d3-42ae-935b-8510f1f76794","order_by":2,"name":"Michiyo Suzuki","email":"","orcid":"","institution":"National Institutes for Quantum Science and Technology (QST)","correspondingAuthor":false,"prefix":"","firstName":"Michiyo","middleName":"","lastName":"Suzuki","suffix":""},{"id":476360897,"identity":"57d42b91-5887-4487-8069-f2e655f38c44","order_by":3,"name":"Hisashi Kitamura","email":"","orcid":"","institution":"National Institutes for Quantum Science and Technology (QST)","correspondingAuthor":false,"prefix":"","firstName":"Hisashi","middleName":"","lastName":"Kitamura","suffix":""}],"badges":[],"createdAt":"2025-06-23 06:53:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6953553/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6953553/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97669620,"identity":"b10e1b05-b7a5-42e2-a5a1-cf702c2be458","added_by":"auto","created_at":"2025-12-08 09:28:33","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":429324,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptSuzukietal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6953553/v1_covered_02525136-7eb5-4982-8223-a432fb3bb29f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"P53-dependent bystander cell-killing effect in human cell lines irradiated with carbon ions","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"bystander cell-killing effect, heavy-ion microbeam, gap-junction mediated cell-to-cell communication, P53 gene","lastPublishedDoi":"10.21203/rs.3.rs-6953553/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6953553/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Since 1994, Phase I/II clinical studies and cancer radiotherapy have used carbon-ion beams at the Heavy Ion Medical Accelerator in Chiba (HIMAC) of the National Institutes for Quantum Science and Technology (QST). Biological effects of direct irradiation for high linear energy transfer (LET) radiation are reported to be higher than those for low-LET X-rays or gamma rays. However, it remains unclear whether indirect biological effects in cells, such as bystander effects, can be described as the ability of cells affected by irradiation to convey manifestations of damage to neighboring cells that are not directly irradiated. In this study, we examined the P53-dependent bystander cell-killing effect in human cells irradiated with either a broad beam or a microbeam of carbon ions. Ten human cell lines of normal origin or cancerous origin with wild-type or mutated type P53-gene status were used in this study. The study results demonstrated an enhanced cell-killing effect by carbon ions—beyond what would be expected based solely on our specific irradiation protocols—in cells with wild-type P53, but not in cells with mutant P53, assuming no bystander effect. 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