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The use of the in vitro micronucleus assay on the genotoxicity assessment of cellulose nanofibrils in mammalian cell lines

dc.contributor.authorVentura, Célia
dc.contributor.authorTeixeira, Sara
dc.contributor.authorMarques, Catarina
dc.contributor.authorVilar, Madalena
dc.contributor.authorPinto, Fátima
dc.contributor.authorLourenço, A.F.
dc.contributor.authorSousa Mendes, A.
dc.contributor.authorFerreira, Paulo J.T.
dc.contributor.authorLouro, Henriqueta
dc.contributor.authorSilva, Maria João
dc.date.accessioned2020-10-28T16:12:21Z
dc.date.available2020-10-28T16:12:21Z
dc.date.issued2020-09-12
dc.description.abstractWith the expansion of innovative cellulose nanofibrils (CNF) applications, either for industrial (e.g., paper industry) or biomedical purposes (e.g., tissue regeneration and dentistry), human exposure has been increasing, raising concerns about their potential health outcomes . Being persistent high aspect-ratio nano-objects, CNFs effects may resemble those of some multi-walled carbon nanotubes, e.g., the MWCNT-7, which has been reported to induce chromosome instability, cytoskeleton alterations and dysfunction of several cancer-related cell signaling pathways . The in vitro cytokinesis-block micronucleus (CBMN) assay is a sensitive and reliable assay for analysis of chromosome damage in mammalian cells, with the potential of providing mechanistic information and predicting carcinogenic effects. In this work we evaluated the use of the CBMN assay in different mammalian cell systems to characterize the genotoxicity of a CNF produced from an industrial bleached Eucalyptus globulus kraft pulp through TEMPO-mediated oxidation followed by a high-pressure homogenization process . The CNF sample was fully characterized in order to assess the most relevant physicochemical properties. It presented a wide distribution of diameters, with the mode in the 20–25 nm range and a length of several micrometers. Preliminary doserange finding through assessment of the cytotoxic effects (MTT and clonogenic assays) in cell lines representative of the respiratory tract (A549, A549 co-cultured with macrophage-like THP-1 cells and V79 cells) and bone (MG63 osteoblasts) showed that the CNF was not cytotoxic, regardless of the exposure period. The results of the CBMN assay (following OECD guideline 487) showed that exposure to low CNF concentrations induced a significant increase of micronuclei in co-cultured alveolar (A549) cells and in osteoblasts, while no significant effect was observed in A549 cells in monoculture. These results support the suitability of the in vitro micronucleus assay to assess the genotoxicity of nanofibers like CNF, highlighting the relevance of the cell system selected. This and other factors related to the experimental design are discussed, pointing to the need of nano-specific guidelines for this assay application in nanogenotoxicology. References Ventura et al. 2020. Cellulose, DOI 10.1007/s10570-020-03176-9 Ventura et al. 2020. Nanotoxicology, 14:479 Ventura et al.2020. Toxicol Lett, 328: 7 Fenech, M. 2007. Nature Protocols 2: 1084. Lourenço et al. 2017. Cellulose 24: 349.pt_PT
dc.description.sponsorshipFCT/MCTES: Project ToxApp4NanoCELFI (PTDC/SAU-PUB/32587/2017) through national funds (PIDDAC), ToxOmics (UIDP/00009/2020) and SFRH/BDE/108095/2015.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/7225
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationA predictive toxicology approach to characterize potential respiratory effects of functionalized nanocellulose fibres in a co-culture system
dc.relationCentre for Toxicogenomics and Human Health
dc.relationImprovement of different paper grades through the use of cellulose nanofibrils
dc.subjectEnvironmental Genotoxicitypt_PT
dc.subjectNanomaterialspt_PT
dc.subjectNanofibrilspt_PT
dc.subjectMicronucleuspt_PT
dc.subjectNanocellulosept_PT
dc.subjectGenotoxicidade Ambientalpt_PT
dc.titleThe use of the in vitro micronucleus assay on the genotoxicity assessment of cellulose nanofibrils in mammalian cell linespt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardTitleA predictive toxicology approach to characterize potential respiratory effects of functionalized nanocellulose fibres in a co-culture system
oaire.awardTitleCentre for Toxicogenomics and Human Health
oaire.awardTitleImprovement of different paper grades through the use of cellulose nanofibrils
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-PUB%2F32587%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00009%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBDE%2F108095%2F2015/PT
oaire.citation.conferencePlace(Virtual meeting)pt_PT
oaire.citation.titleEnvironmental Mutagenesis & Genomics Society Virtual Annual Meeting (EMGS), 12-16 September 2020pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameLouro
person.familyNameSilva
person.givenNameHenriqueta
person.givenNameMaria Joao
person.identifier157627
person.identifier.ciencia-id721D-2BB1-7DB1
person.identifier.ciencia-id7710-643D-97A3
person.identifier.orcid0000-0001-9744-7332
person.identifier.orcid0000-0002-6060-0716
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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