Transcriptomic Analysis Reveals the Synergistic Mechanisms of Arsenic-Induced DNA Damage and Cell Apoptosis in Pancreatic β-cells

Transcriptomic Analysis Reveals the Synergistic Mechanisms of Arsenic-Induced DNA Damage and Cell Apoptosis in Pancreatic β-cells | 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 Transcriptomic Analysis Reveals the Synergistic Mechanisms of Arsenic-Induced DNA Damage and Cell Apoptosis in Pancreatic β-cells Jiamin YUAN, Rongxian LI, Zuoshun HE, Zhiqiong YUAN, Shiyan GU This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8691493/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 13 You are reading this latest preprint version Abstract Arsenic is a widely existing environmental pollutant that induces Pancreatic β-cells and promotes the development of type 2 diabetes mellitus (T2DM). However, the molecular mechanism by which arsenic exposure leads to Pancreatic β-cell death has not been fully elucidated. In this study, pancreatic β-cell line, INS-1 cells, were treated with sodium arsenite (NaAsO 2 ) to assess cell death and DNA damage, combined with transcriptome sequencing to investigate the underlying molecular mechanisms. The data indicated that arsenic treatment decreased INS-1 cell viability, increased apoptosis rates, disrupted the balance of apoptosis-related proteins, and elevated the DNA damage marker 8-hydroxy-2’-deoxyguanosine (8-OHdG). Transcriptome analysis identified 8,341 differentially expressed genes, including 5,072 up-regulated and 3,269 down-regulated genes. Enrichment analysis showed that up-regulated genes were mainly enriched in cytochrome P450 (CYP450) metabolism and chemical carcinogen-DNA adduct pathways, while down-regulated genes were primarily enriched in DNA repair pathways. The findings from the Western blot analysis demonstrated that there was an up-regulation of protein levels for Cyp2e1 and Gsta2, both of which are integral components of the CYP450 metabolic pathway. In conclusion, our findings indicate that arsenic exposure concurrently impairs cellular detoxification functions and hinders DNA repair mechanisms, thereby synergistically inducing apoptosis in pancreatic β-cells. Arsenic Pancreaticβ-cells Apoptosis Cell death DNA damage Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 18 Feb, 2026 Reviews received at journal 16 Feb, 2026 Reviews received at journal 15 Feb, 2026 Reviews received at journal 11 Feb, 2026 Reviewers agreed at journal 27 Jan, 2026 Reviewers agreed at journal 26 Jan, 2026 Reviewers agreed at journal 26 Jan, 2026 Reviewers agreed at journal 26 Jan, 2026 Reviewers agreed at journal 26 Jan, 2026 Reviewers invited by journal 26 Jan, 2026 Editor assigned by journal 26 Jan, 2026 Submission checks completed at journal 26 Jan, 2026 First submitted to journal 25 Jan, 2026 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-8691493","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":581392553,"identity":"73546d4a-516f-424f-ae68-89fea87e34db","order_by":0,"name":"Jiamin YUAN","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Jiamin","middleName":"","lastName":"YUAN","suffix":""},{"id":581392554,"identity":"803266c2-502f-4542-b734-1e0a1745868f","order_by":1,"name":"Rongxian LI","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Rongxian","middleName":"","lastName":"LI","suffix":""},{"id":581392555,"identity":"2b2b224f-ccee-43df-af1d-2195e2b07e69","order_by":2,"name":"Zuoshun HE","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Zuoshun","middleName":"","lastName":"HE","suffix":""},{"id":581392556,"identity":"58cd95cc-2906-443e-9d28-66270158cea9","order_by":3,"name":"Zhiqiong YUAN","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Zhiqiong","middleName":"","lastName":"YUAN","suffix":""},{"id":581392557,"identity":"80759324-ef11-42be-9e13-793428134788","order_by":4,"name":"Shiyan GU","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYJAC5j8V/+XY2NsPkKCH5wyzMR/PmQQStPC2MSfOk3AwIE61wfnlzyQk2NjS2yQYEhh+VGwjQsuNN2YSBjw8uW3SjQcYe87cJkbLGTaJBAmJ3DaZAwnMjG1EaTn+TOKAgUE6UKMBkVrON5hJNiQkJBCvRfIGj7E1w4EDhm3AQD5IlF/4zh9/eJvx3wF5+fb2gw9+VBChReFGAosEjHOAsHogkO8/wPyBKJWjYBSMglEwcgEARcM+cjPvJbcAAAAASUVORK5CYII=","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Shiyan","middleName":"","lastName":"GU","suffix":""}],"badges":[],"createdAt":"2026-01-25 09:39:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8691493/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8691493/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101751738,"identity":"6b649afb-7fbd-453e-81fd-b52a6b2fd031","added_by":"auto","created_at":"2026-02-03 10:23:02","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2021725,"visible":true,"origin":"","legend":"","description":"","filename":"1.20MolecularMechanismsofArsenicInducedDeathinRatINS1Cells4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8691493/v1_covered_83c2e64b-12ed-481f-b2a6-4d526c03640c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Transcriptomic Analysis Reveals the Synergistic Mechanisms of Arsenic-Induced DNA Damage and Cell Apoptosis in Pancreatic β-cells","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"biological-trace-element-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bter","sideBox":"Learn more about [Biological Trace Element Research](https://www.springer.com/journal/12011)","snPcode":"12011","submissionUrl":"https://submission.nature.com/new-submission/12011/3","title":"Biological Trace Element Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Arsenic, Pancreaticβ-cells, Apoptosis, Cell death, DNA damage","lastPublishedDoi":"10.21203/rs.3.rs-8691493/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8691493/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eArsenic is a widely existing environmental pollutant that induces Pancreatic β-cells and promotes the development of type 2 diabetes mellitus (T2DM). However, the molecular mechanism by which arsenic exposure leads to Pancreatic β-cell death has not been fully elucidated. In this study, pancreatic β-cell line, INS-1 cells, were treated with sodium arsenite (NaAsO\u003csub\u003e2\u003c/sub\u003e) to assess cell death and DNA damage, combined with transcriptome sequencing to investigate the underlying molecular mechanisms. The data indicated that arsenic treatment decreased INS-1 cell viability, increased apoptosis rates, disrupted the balance of apoptosis-related proteins, and elevated the DNA damage marker 8-hydroxy-2\u0026rsquo;-deoxyguanosine (8-OHdG). Transcriptome analysis identified 8,341 differentially expressed genes, including 5,072 up-regulated and 3,269 down-regulated genes. Enrichment analysis showed that up-regulated genes were mainly enriched in cytochrome P450 (CYP450) metabolism and chemical carcinogen-DNA adduct pathways, while down-regulated genes were primarily enriched in DNA repair pathways. 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In conclusion, our findings indicate that arsenic exposure concurrently impairs cellular detoxification functions and hinders DNA repair mechanisms, thereby synergistically inducing apoptosis in pancreatic β-cells.\u003c/p\u003e","manuscriptTitle":"Transcriptomic Analysis Reveals the Synergistic Mechanisms of Arsenic-Induced DNA Damage and Cell Apoptosis in Pancreatic β-cells","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-29 18:20:39","doi":"10.21203/rs.3.rs-8691493/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-18T06:53:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-16T08:27:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-15T12:46:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-11T17:10:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"74704614924292910784018302782791138419","date":"2026-01-27T19:35:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"30420183707219647534531904707544254592","date":"2026-01-27T02:25:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"314132973957946709961584890327544460447","date":"2026-01-27T01:49:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"310405300079388001312847507140314658099","date":"2026-01-27T00:15:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"168121645456105218219615589355769899254","date":"2026-01-26T23:31:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-26T22:47:23+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-26T16:02:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-26T09:25:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"Biological Trace Element Research","date":"2026-01-25T09:24:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"biological-trace-element-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bter","sideBox":"Learn more about [Biological Trace Element Research](https://www.springer.com/journal/12011)","snPcode":"12011","submissionUrl":"https://submission.nature.com/new-submission/12011/3","title":"Biological Trace Element Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f791d68c-c7f9-4133-b5fd-0e7911924c4e","owner":[],"postedDate":"January 29th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-02-18T07:09:00+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-29 18:20:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8691493","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8691493","identity":"rs-8691493","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}