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Effects of TiO2 Nanoparticles on the Genome-Wide Methylation of Human Epithelial Intestinal Cells

2023-11-17Conference object Restricted access
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dc.contributor.authorValente, Ana
dc.contributor.authorVieira, Luís
dc.contributor.authorSilva, Catarina
dc.contributor.authorLouro, Henriqueta
dc.contributor.authorSilva, Maria João
dc.contributor.authorVentura, Célia
dc.date.accessioned2024-02-06T10:43:10Z
dc.date.available2024-02-06T10:43:10Z
dc.date.issued2023-11-17
dc.description.abstractIntroduction: Titanium dioxide nanoparticles (TiO2NP) have multiple applications in industry (e.g., engineering, cosmetics, food additives), and biomedicine (e.g., targeted drug delivery and biosensing). Food-grade TiO2 (E171) is applied as a food additive to whiten and improve the opacity of food products, while also having the ability to enhance its flavour. In 2021, EU member states banned E171 from all food products, since there is doubts about its genotoxicity. Nevertheless, the ingestion of TiO2NPs may still occur through to other sources, such as contaminated food or water, consumer products (e.g., toothpaste and lipstick) or pharmaceutics. To date, there is some in vitro evidence that TiO2NP may induce changes in DNA methylation. However, very few studies were performed, and none used genome-wide approaches to identify possible differentially methylated genes induced by TiO2NP exposure, and its impact on molecular pathways. Methodology: Caco-2 epithelial intestinal cells were exposed to 14 μg/ml of anatase, rutile or brookite phase TiO2NP for 24h. Genomic DNA was extracted from exposed and non-exposed cells. DNA libraries were generated using the Premium Reduced Representative Bisulfite Sequencing (RRBS) kit (Diagenode) and sequenced on the NextSeq 550 system (Illumina) using 100 bp paired reads. The Galaxy platform was used for read treatment and mapping, methylation calling and assessing of differentially methylated regions between exposed and non-exposed cells. Pathway analysis was performed using Reactome, and gene ontology analysis with the ClueGO plugin in Cytoscape. Results: Significant differential methylation (p ≤ 0.05) of 92 genes (21 hyper- and 71 hypo-methylated), 70 genes (12 hyper- and 58 hypo-methylated) and 88 genes (21 hyper- and 67 hypo-methylated) was observed for the anatase, rutile and brookite phase TiO2NP, respectively. Functional pathway analysis of these methylation changes identified several relevant cellular pathways that may be altered by exposure, such as G alpha signalling events, being some associated to colon cancer. Conclusions: All types of TiO2NP induce changes in genome methylation of intestinal cells, which may affect cell proliferation, differentiation and survival. Moreover, although some dysfunctional pathways are shared between the three TiO2NP, many are type-specific, suggesting different molecular mechanisms of action for each TiO2NP.pt_PT
dc.description.sponsorshipFunding: FCT (PTDC/SAU-PUB/29481/2017), FCT UIDB/00009/2020 UIDP/00009/2020.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/9041
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationCellular and Molecular Mechanisms of Toxicity of Ingested Nanomaterials
dc.relationCentre for Toxicogenomics and Human Health
dc.relationCentre for Toxicogenomics and Human Health
dc.subjectTitanium dioxidept_PT
dc.subjectNanoparticlespt_PT
dc.subjectEnvironmental Genotoxicitypt_PT
dc.subjectGenotoxicidade Ambientalpt_PT
dc.titleEffects of TiO2 Nanoparticles on the Genome-Wide Methylation of Human Epithelial Intestinal Cellspt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardTitleCellular and Molecular Mechanisms of Toxicity of Ingested Nanomaterials
oaire.awardTitleCentre for Toxicogenomics and Human Health
oaire.awardTitleCentre for Toxicogenomics and Human 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/UIDB%2F00009%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00009%2F2020/PT
oaire.citation.conferencePlaceLisboa, Portugalpt_PT
oaire.citation.title3rd GenomePT Symposium 2023 - Symposium of the National Research infrastructure for Genome Sequencing and Analysis, 10 outubro 2023pt_PT
oaire.fundingStreamConcurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2017
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameLouro
person.familyNameSilva
person.familyNameVentura
person.givenNameHenriqueta
person.givenNameMaria Joao
person.givenNameCélia
person.identifier157627
person.identifier2056460
person.identifier.ciencia-id721D-2BB1-7DB1
person.identifier.ciencia-id7710-643D-97A3
person.identifier.ciencia-id6116-89BA-C617
person.identifier.orcid0000-0001-9744-7332
person.identifier.orcid0000-0002-6060-0716
person.identifier.orcid0000-0002-0637-2222
person.identifier.scopus-author-id6507971479
person.identifier.scopus-author-id55944437600
project.funder.identifierhttp://doi.org/10.13039/501100001871
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
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
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