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Ingested titanium dioxide nanomaterials: new approach to investigate intestinal genotoxicity and key cellular/molecular effects

dc.contributor.authorVentura, Célia
dc.contributor.authorRolo, Dora
dc.contributor.authorGramacho, Ana C.
dc.contributor.authorVieira, Adriana
dc.contributor.authorRoque, Rossana
dc.contributor.authorValente, Ana
dc.contributor.authorVital, Nádia
dc.contributor.authorPinto, Fátima
dc.contributor.authorAlvito, Paula
dc.contributor.authorAssunção, Ricardo
dc.contributor.authorMartins, Carla
dc.contributor.authorBettencourt, Ana
dc.contributor.authorGonçalves, Lídia
dc.contributor.authorPereira, Joana
dc.contributor.authorMatos, Paulo
dc.contributor.authorJordan, Peter
dc.contributor.authorVieira, Luís
dc.contributor.authorSilva, Catarina
dc.contributor.authorSilva, Maria Joao
dc.contributor.authorLouro, Henriqueta
dc.date.accessioned2026-03-04T12:58:08Z
dc.date.available2026-03-04T12:58:08Z
dc.date.issued2025-06
dc.descriptionAbstract disponível em: Book of Abstracts of the 53rd EEMGS Congress / 47th Annual CSSMC Meeting (EEMGS/CSSMC 2025); 2025 Jun 2–5; Bratislava, Slovak Republic. p. 26.
dc.description.abstractOral exposure to titanium dioxide nanomaterials (TiO2NMs) is due to their presence in food, food contact materials, medicines and cosmetics. The gastrointestinal tract(GIT) represents primary site of contact, that may result in systemic exposure, if biological barriers are surpassed. The INGESTnano project aimed to investigate nano-bio interactions at the cellular/molecular levels within the context of the intestinal tract and digestion processes, for understanding potential effects on human health. A group of three TiO₂NMs(NM-102, NM-103, NM-105) was selected as case study using a new approach methodology(NAM), incorporating the in vitro human digestion simulation prior to biological assays in Caco-2 and HT29-MTX-E12 intestinal cells. The endpoints included cyto- and genotoxicity, cell uptake, intestinal permeability, GIT transport and epigenomic modifications. The results showed a more pronounced cytotoxicity in HT29-MTX-E12 cells for digested NM-105, as compared to undigested, concomitantly with subtle changes in hydrodynamic-size. DNA-damage induction was more relevant for NM-105, and the micronucleus assay showed chromosomal damage in HT29-MTX-E12 cells for all TiO2NMs, especially after in vitro digestion.All NMs, digested or not, were internalized by intestinal cells, but did not affect transepithelial resistance, nor the epithelial markers in polarized enterocytes. NM-102 was retained in lysosomes, while NM-103 and NM-105 showed transcytosis, a potential gateway for systemic distribution. Using Reduced Representation Bisulfite Sequencing, several differentially methylated genes were identified for the TiO₂NMs, either digested or not. Pathway and Gene Ontology analyses showed that each TiO2NMs has a different functional impact on intestinal cells, probably linked to specific physicochemical properties, and digestion seems to reduce this impact. A trend towards CpG hypermethylation was observed upon NM-105 exposure, unlike for the other TiO2NMs. This integrated approach enabled the identification of key events and molecular pathways elicited by TiO2NMs, highlighting the importance of considering the digestion on the induction of adverse outcomes.eng
dc.description.sponsorshipFunded by FCT/MCTES through INGESTnano - PTDC/SAU-PUB/29481/2017
dc.identifier.urihttp://hdl.handle.net/10400.18/11113
dc.language.isoeng
dc.peerreviewedno
dc.relationCellular and Molecular Mechanisms of Toxicity of Ingested Nanomaterials
dc.relation.hasversionhttps://eemgs.eu/wp-content/uploads/2025/06/EEMGS-CSSMC-2025-book-of-abstracts-FINAL.pdf
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectFood Safety
dc.subjectEnvironmental Genotoxicity
dc.subjectNanomaterials
dc.subjectToxicologia Alimentar
dc.subjectGenotoxicidade Ambiental
dc.subjectSegurança Alimentar
dc.titleIngested titanium dioxide nanomaterials: new approach to investigate intestinal genotoxicity and key cellular/molecular effectseng
dc.typeconference object
dspace.entity.typePublication
oaire.awardNumberPTDC/SAU-PUB/29481/2017
oaire.awardTitleCellular and Molecular Mechanisms of Toxicity of Ingested Nanomaterials
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.citation.conferenceDate2025-06-02
oaire.citation.conferencePlaceBratislava, Slovak Republic
oaire.citation.title53rd European Environmental Mutagenesis and Genomics Society (EEMGS) Meeting, 2–5 June 2025
oaire.fundingStreamConcurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2017
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.nameFundação para a Ciência e a Tecnologia
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relation.isAuthorOfPublicationa7763685-7c34-468d-b958-9dd0aca66db4
relation.isAuthorOfPublication2361a951-8b9a-4b90-92d6-f6384003a242
relation.isAuthorOfPublication.latestForDiscoveryfa89f42b-12a4-47bd-a4fb-0f65cbc06885
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