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Genome-wide methylation changes upon Caco-2 cells exposure to undigested and digested titanium dioxide nanoparticles

2025-11-25Artigo científico Acesso restrito
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dc.contributor.authorVentura, Célia
dc.contributor.authorValente, Ana
dc.contributor.authorVieira, Luís
dc.contributor.authorSilva, Catarina
dc.contributor.authorRolo, Dora
dc.contributor.authorSilva, Maria Joao
dc.contributor.authorLouro, Henriqueta
dc.date.accessioned2026-01-20T15:44:53Z
dc.date.available2026-01-20T15:44:53Z
dc.date.issued2025-11-25
dc.description.abstractIntroduction: Titanium dioxide nanoparticles (TiO2NPs) are relevant nanomaterials (NMs) for biomedicine and industry, which raise concerns about its effects on human health, particularly through ingestion. Several studies found that exposure to NMs can lead to DNA methylation changes. DNA methylation regulates gene expression, playing a vital role in development and disease, with aberrant methylation linked to cancer and other health conditions. Aim: We aimed at identifying DNA methylation changes in intestinal cells exposed to three TiO2NPs (NM-102, NM-103, NM-105), either digested or undigested. Their cellular effects were investigated by functional pathway and gene ontology (GO) analysis. Results: 48, 41, 55 differentially methylated genes (DMG) were identified after exposure to undigested NM-102, NM-103, NM-105; 71, 65, 55 DMG in the digested counterparts. Undigested TiO2NPs affected many G-proteins/adenylate cyclase-related pathways (PKA, glucagon, GPER1, CREB1, ADORA2B); the digested had lower impact. Cancer-related pathways were shared. Enriched molecular functions were mainly transcription-related; different biological processes were enriched if TiO2NPs were digested or not. Conclusions: TiO2NPs exposure causes DNA methylation changes that have a functional impact on intestinal cells, which differs with its physicochemical properties and digestion. NM-105 caused hypermethylation, unlike the other TiO2NPs. This study highlights DNA methylation relevance in assessing NMs’ toxicity.eng
dc.description.abstractPlain language summary: Titanium dioxide nanoparticles (TiO2NP) are widely present in our daily lives, including in food as a white pigment to make it better-looking and appealing. Although there are many toxicological studies on TiO2NP, few have focused on its effects on DNA methylation, which is a mechanism for regulating gene expression, and consequently, cellular functions. In this study, human intestinal cells were exposed to three different types of TiO2NP, before and after simulated digestion. Our results indicate that the physical-chemical characteristics of TiO2NP influence its effects and demonstrate the impact of digestion, relevant in the context of oral exposure. Moreover, they highlight the biological impact of TiO2NP on intestinal cells through DNA methylation changes and, consequently, the relevance of studying these changes when assessing the adverse effects of nanomaterials on human health.eng
dc.description.abstractHighlights: - TiO2NPs exposure caused DNA methylation changes on intestinal cells. - Simulated digestion of TiO2NPs caused methylation differences compared to undigested TiO2NPs. - Undigested TiO2NPs mainly affected G-proteins and adenylate cyclase pathways, while digested have a less obvious impact; both affected cancer-related pathways. - TiO2NPs with different physicochemical properties induced different DNA methylation changes. - NM-105 caused DNA hypermethylation, unlike the other TiO2NPs. - DNA methylation studies are relevant for assessing nanomaterials’ toxicity.eng
dc.description.sponsorshipThis work was funded by the Portuguese Foundation for Science and Technology FCT/MCTES through national funds (PIDDAC), [PTDC/SAUPUB/29481/2017] and co-funded by [UID/04923] - Comprehensive Health Research Centre, through national funds.
dc.identifier.citationEpigenomics. 2025 Dec;17(18):1381-1397. doi: 10.1080/17501911.2025.2593814. Epub 2025 Nov 25
dc.identifier.doi10.1080/17501911.2025.2593814
dc.identifier.eissn1750-192X
dc.identifier.issn1750-1911
dc.identifier.pmid41289081
dc.identifier.urihttp://hdl.handle.net/10400.18/10727
dc.language.isoeng
dc.peerreviewedyes
dc.publisherTaylor and Francis Group
dc.relationCellular and Molecular Mechanisms of Toxicity of Ingested Nanomaterials
dc.relationComprehensive Health Research Center - Research, Education, Training and Innovation in Clinical research and Public Health
dc.relation.hasversionhttps://www.tandfonline.com/doi/full/10.1080/17501911.2025.2593814
dc.relation.ispartofEpigenomics
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectEnvironmental Genotoxicity
dc.subjectDNA Methylation
dc.subjectGene Ontology
dc.subjectNanomaterials
dc.subjectPathway Analysis
dc.subjectSimulated Digestion
dc.subjectGenotoxicidade Ambiental
dc.titleGenome-wide methylation changes upon Caco-2 cells exposure to undigested and digested titanium dioxide nanoparticleseng
dc.typejournal article
dcterms.referenceshttps://www.tandfonline.com/doi/suppl/10.1080/17501911.2025.2593814?scroll=top
dspace.entity.typePublication
oaire.awardTitleCellular and Molecular Mechanisms of Toxicity of Ingested Nanomaterials
oaire.awardTitleComprehensive Health Research Center - Research, Education, Training and Innovation in Clinical research and Public Health
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2017/PTDC%2FSAU-PUB%2F29481%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04923%2F2020/PT
oaire.citation.endPage1397
oaire.citation.issue18
oaire.citation.startPage1381
oaire.citation.titleEpigenomics
oaire.citation.volume17
oaire.fundingStreamConcurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2017
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameVentura
person.familyNameSilva
person.familyNameLouro
person.givenNameCélia
person.givenNameMaria Joao
person.givenNameHenriqueta
person.identifier2056460
person.identifier157627
person.identifier.ciencia-id6116-89BA-C617
person.identifier.ciencia-id7710-643D-97A3
person.identifier.ciencia-id721D-2BB1-7DB1
person.identifier.orcid0000-0002-0637-2222
person.identifier.orcid0000-0002-6060-0716
person.identifier.orcid0000-0001-9744-7332
person.identifier.scopus-author-id55944437600
person.identifier.scopus-author-id6507971479
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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