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Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes

dc.contributor.authorBramatti, Isabella
dc.contributor.authorMatos, Beatriz
dc.contributor.authorFigueiredo, Neusa
dc.contributor.authorPousão-Ferreira, Pedro
dc.contributor.authorBranco, Vasco
dc.contributor.authorMartins, Marta
dc.contributor.institutionMARE - Centro de Ciências do Mar e do Ambiente
dc.contributor.institutionDCEA - Departamento de Ciências e Engenharia do Ambiente
dc.contributor.pblElsevier
dc.date.accessioned2023-07-07T22:18:14Z
dc.date.available2023-07-07T22:18:14Z
dc.date.issued2023-01-10
dc.descriptionFunding Information: This work was funded by Fundação para a Ciência e Tecnologia (FCT; www.fct.pt ) with the following grants: i) Vasco Branco is financed through Norma Transitória - DL57/2016/CP1376/CT002 ; ii) Marta Martins is financed through the Scientific Employment Stimulus - Institutional Call ( CEECINST/00102/2018 ). Neusa Figueiredo is financed by FCT via the PAHMIX project ( NOVAID39 ). We thank Marisa Barata from IPMA, Joana Neves and Joana Antunes from MARE – FCT NOVA for fish maintenance and transport. Publisher Copyright: © 2022
dc.description.abstractPolycyclic Aromatic Hydrocarbons (PAHs) are persistent pollutants normally found in the environment as complex mixtures. Although several individual PAHs are classified as mutagenic and carcinogenic pollutants, the interaction effects between compounds in a mixture may trigger different toxicological mechanisms and, consequently, yield different effects to organisms which are not accounted for in risk assessment guidelines. Given the ubiquity of PAHs, understanding the mechanistic features of their mixtures is a pressing research need. Therefore, the present work aimed to disclose the interaction effects of three PAHs with different carcinogenic potential and chemical structure, in primary hepatocyte cells of gilt-headed seabreams (Sparus aurata). Hepatocytes were exposed to Phenanthrene (Phe), Benzo[a]pyrene (B[a]P) and Benzo[b]fluoranthene (B[b]F) and their mixtures at different proportions and several cellular responses were analyzed: cellular viability, CYP1A1 activity (EROD assay) and protein expression level (Western blot); transcript (mRNA) levels of CYP1A1, EPXH1 and GST-3 (qRT-PCR); genotoxic effects (DNA strand breakage) by the Comet assay. Results show that B[a]P induced CYP1A1 gene and protein expression increasing its activity and, therefore, increasing the production of metabolites that trigger genotoxic DNA damage (%). Most importantly, mixtures containing Phe and B[a]P increased even further CYP1A1 mRNA levels and DNA damage (up to 70 %) which suggests that, although Phe is considered a non-carcinogenic PAH, it potentiates CYP1A1 synthesis induced by B[a]P, increasing its genotoxicity. These findings indicate that the upregulation of CYP1A1 by carcinogenic PAHs will not weaken even when in mixtures with non-carcinogenic PAHs. On contrary, non-carcinogenic PAHs may potentiate the genotoxic effect of carcinogenic PAH and therefore mixture composition should be taken in account when assessing PAH toxicity. In fact, our results point to the need of redefining Environmental Risk Assessment protocols for mixtures of carcinogenic pollutants.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent8
dc.format.extent1422611
dc.identifier.doi10.1016/j.scitotenv.2022.158783
dc.identifier.issn0048-9697
dc.identifier.otherPURE: 65670637
dc.identifier.otherPURE UUID: 08bf9a66-677a-4e21-a633-dc8233cda38d
dc.identifier.otherScopus: 85138442155
dc.identifier.otherWOS: 000911393100001
dc.identifier.otherPubMed: 36116656
dc.identifier.urihttp://hdl.handle.net/10362/154986
dc.identifier.urlhttps://www.scopus.com/pages/publications/85138442155
dc.language.isoeng
dc.peerreviewedyes
dc.relationinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCTA-AMB%2F29173%2F2017/PT
dc.relationMixtures of Environmental Carcinogens: a molecular approach to improve environmental risk assessment strategies.
dc.relationMarine and Environmental Sciences Centre
dc.relationAquatic Research Infrastructure Network
dc.relationResearch Institute for Medicines
dc.relationResearch Institute for Medicines
dc.relationMolecular Insight on the Toxicity of Mixtures of Polycyclic Aromatic Hydrocarbons to Improve Environmental Guidelines
dc.relationinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04138%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/OE/2020.09005.BD/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCTA-AMB%2F29173%2F2017/PT
dc.subjectBenzo[a]pyrene
dc.subjectBenzo[b]fluoranthene
dc.subjectCYP1A1
dc.subjectDNA strand breakage
dc.subjectPhenanthrene
dc.subjectEnvironmental Engineering
dc.subjectEnvironmental Chemistry
dc.subjectWaste Management and Disposal
dc.subjectPollution
dc.titleInteraction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytesen
dc.title.subtitleFrom molecular mechanisms to genotoxic effectsen
dc.typejournal article
degois.publication.titleScience of the Total Environment
degois.publication.volume855
dspace.entity.typePublication
oaire.awardNumberPTDC/CTA-AMB/29173/2017
oaire.awardNumberUIDB/04292/2020
oaire.awardNumberLA/P/0069/2020
oaire.awardNumberUIDB/04138/2020
oaire.awardNumberUIDP/04138/2020
oaire.awardNumber2020.09005.BD
oaire.awardTitleMixtures of Environmental Carcinogens: a molecular approach to improve environmental risk assessment strategies.
oaire.awardTitleMarine and Environmental Sciences Centre
oaire.awardTitleAquatic Research Infrastructure Network
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleMolecular Insight on the Toxicity of Mixtures of Polycyclic Aromatic Hydrocarbons to Improve Environmental Guidelines
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCTA-AMB%2F29173%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04292%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0069%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/2020.09005.BD/PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
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oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamOE
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