Publicação
Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects
| Resumo: | Polycyclic 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. |
|---|---|
| Autores principais: | Bramatti, Isabella |
| Outros Autores: | Matos, Beatriz; Figueiredo, Neusa; Pousão-Ferreira, Pedro; Branco, Vasco; Martins, Marta |
| Assunto: | CYP1A1 DNA strand breakage Phenanthrene Benzo[a]pyrene Benzo[b]fluoranthene |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1866809994917183488 |
|---|---|
| author | Bramatti, Isabella |
| author2 | Matos, Beatriz Figueiredo, Neusa Pousão-Ferreira, Pedro Branco, Vasco Martins, Marta |
| author2_role | author author author author author |
| author_facet | Bramatti, Isabella Matos, Beatriz Figueiredo, Neusa Pousão-Ferreira, Pedro Branco, Vasco Martins, Marta |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Bramatti, Isabella\"},{\"Person.name\":\"Matos, Beatriz\",\"Person.identifier.orcid\":\"0000-0001-5923-5849\"},{\"Person.name\":\"Figueiredo, Neusa\",\"Person.identifier.orcid\":\"0000-0003-0062-1117\"},{\"Person.name\":\"Pousão-Ferreira, Pedro\",\"Person.identifier.orcid\":\"0000-0001-6746-764X\"},{\"Person.name\":\"Branco, Vasco\",\"Person.identifier.orcid\":\"0000-0002-0466-4934\"},{\"Person.name\":\"Martins, Marta\",\"Person.identifier.orcid\":\"0000-0002-3818-6256\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Bramatti, Isabella Matos, Beatriz Figueiredo, Neusa Pousão-Ferreira, Pedro Branco, Vasco Martins, Marta |
| datacite.date.Accepted.fl_str_mv | 2023-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2023-08-16T13:59:08Z |
| datacite.date.embargoed.fl_str_mv | 2023-08-16T13:59:08Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | CYP1A1 DNA strand breakage Phenanthrene Benzo[a]pyrene Benzo[b]fluoranthene |
| datacite.titles.title.fl_str_mv | Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Bramatti, Isabella Matos, Beatriz Figueiredo, Neusa Pousão-Ferreira, Pedro Branco, Vasco Martins, Marta |
| dc.date.Accepted.fl_str_mv | 2023-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2023-08-16T13:59:08Z |
| dc.date.embargoed.fl_str_mv | 2023-08-16T13:59:08Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/58891 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | CYP1A1 DNA strand breakage Phenanthrene Benzo[a]pyrene Benzo[b]fluoranthene |
| dc.title.fl_str_mv | Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Polycyclic 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/5c9e585e-8ec1-4553-bf06-09307e832840/download |
| funding.funder.alternateName_str_mv | FCT FCT FCT FCT FCT |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia |
| funding.name_str_mv | 3599-PPCDT 6817 - DCRRNI ID 6817 - DCRRNI ID 6817 - DCRRNI ID OE |
| id | ul_7fd7cd908b08fa1fe85b7ea04eb5bcee |
| identifier.url.fl_str_mv | http://hdl.handle.net/10451/58891 |
| instacron_str | ul |
| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
| network_acronym_str | ul |
| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/58891 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Bramatti, Isabella Bramatti, Isabella https://www.ciencia-id.pt/D41D-0E82-B973 D41D-0E82-B973 Matos, Beatriz Matos, Beatriz https://www.ciencia-id.pt/9418-6989-B909 9418-6989-B909 http://orcid.org/0000-0001-5923-5849 0000-0001-5923-5849 Figueiredo, Neusa Figueiredo, Neusa https://www.ciencia-id.pt/341E-8FD2-22E2 341E-8FD2-22E2 http://orcid.org/0000-0003-0062-1117 0000-0003-0062-1117 Pousão-Ferreira, Pedro Pousão-Ferreira, Pedro https://www.ciencia-id.pt/5A11-AB29-0849 5A11-AB29-0849 http://orcid.org/0000-0001-6746-764X 0000-0001-6746-764X Branco, Vasco Branco, Vasco https://www.ciencia-id.pt/671C-816B-F077 671C-816B-F077 http://orcid.org/0000-0002-0466-4934 0000-0002-0466-4934 Martins, Marta Martins, Marta https://www.ciencia-id.pt/7810-1C0F-20D4 7810-1C0F-20D4 http://orcid.org/0000-0002-3818-6256 0000-0002-3818-6256 |
| publishDate | 2023 |
| publisher.none.fl_str_mv | Elsevier |
| reponame_str | Repositório da Universidade de Lisboa |
| repository_id_str | urn:repositoryAcronym:ul |
| service_str_mv | urn:repositoryAcronym:ul |
| spelling | engElsevierpt_PTPolycyclic 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.application/pdfpt_PTInteraction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effectsPersonalBramatti, IsabellaDSpacehttp://dspace.org/items/5dcedc64-f9dd-4be1-b228-b5db6fc5cb95DSpacehttp://dspace.org/items/5dcedc64-f9dd-4be1-b228-b5db6fc5cb95Calvo BramattiIsabellaCiência IDhttps://www.ciencia-id.ptD41D-0E82-B973PersonalMatos, BeatrizDSpacehttp://dspace.org/items/9153b0eb-d3cd-4312-9c34-998f2a5c315bDSpacehttp://dspace.org/items/9153b0eb-d3cd-4312-9c34-998f2a5c315bManso de MatosBeatrizCiência IDhttps://www.ciencia-id.pt9418-6989-B909ORCIDhttp://orcid.org0000-0001-5923-5849PersonalFigueiredo, NeusaDSpacehttp://dspace.org/items/d2740563-4af4-406c-8e14-af87e66aca63DSpacehttp://dspace.org/items/d2740563-4af4-406c-8e14-af87e66aca63Loureiro Figueiredo MotubaneNeusa LindorosaCiência IDhttps://www.ciencia-id.pt341E-8FD2-22E2ORCIDhttp://orcid.org0000-0003-0062-1117PersonalPousão-Ferreira, PedroDSpacehttp://dspace.org/items/a239f428-e26c-4cc4-b490-f6caea01767eDSpacehttp://dspace.org/items/a239f428-e26c-4cc4-b490-f6caea01767eMarques Pousão-FerreiraPedroCiência IDhttps://www.ciencia-id.pt5A11-AB29-0849ORCIDhttp://orcid.org0000-0001-6746-764XScopus Author IDhttps://www.scopus.com6506349877PersonalBranco, VascoDSpacehttp://dspace.org/items/06d8e0eb-35e5-4d30-90d8-5af2fdab414bDSpacehttp://dspace.org/items/06d8e0eb-35e5-4d30-90d8-5af2fdab414bVeloso Neves BrancoVasco RuiCiência IDhttps://www.ciencia-id.pt671C-816B-F077ORCIDhttp://orcid.org0000-0002-0466-4934Scopus Author IDhttps://www.scopus.com8271087300PersonalMartins, MartaDSpacehttp://dspace.org/items/1edab515-0acc-4dc8-b94e-eb44cad2538cDSpacehttp://dspace.org/items/1edab515-0acc-4dc8-b94e-eb44cad2538cMartinsMartaCiência IDhttps://www.ciencia-id.pt7810-1C0F-20D4ORCIDhttp://orcid.org0000-0002-3818-6256Scopus Author IDhttps://www.scopus.com35603849900HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptDOIIsPartOf10.1016/J.SCITOTENV.2022.1587832023-08-16T13:59:08Z20232022-11-22T12:08:52Z2023-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/58891http://purl.org/coar/access_right/c_abf2open accessCYP1A1DNA strand breakagePhenanthreneBenzo[a]pyreneBenzo[b]fluoranthene1364945 bytesFundação para a Ciência e a TecnologiaMixtures of Environmental Carcinogens: a molecular approach to improve environmental risk assessment strategies.3599-PPCDTCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaMarine and Environmental Sciences Centre6817 - DCRRNI IDCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaResearch Institute for Medicines6817 - DCRRNI IDCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaResearch Institute for Medicines6817 - DCRRNI IDCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaMolecular Insight on the Toxicity of Mixtures of Polycyclic Aromatic Hydrocarbons to Improve Environmental GuidelinesOECrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal article2023http://creativecommons.org/licenses/by-nc-nd/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/5c9e585e-8ec1-4553-bf06-09307e832840/downloadScience of the Total Environment855158783 |
| spellingShingle | Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects Bramatti, Isabella CYP1A1 DNA strand breakage Phenanthrene Benzo[a]pyrene Benzo[b]fluoranthene |
| status | SINGLETON |
| subject.fl_str_mv | CYP1A1 DNA strand breakage Phenanthrene Benzo[a]pyrene Benzo[b]fluoranthene |
| title | Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects |
| title_full | Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects |
| title_fullStr | Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects |
| title_full_unstemmed | Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects |
| title_short | Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects |
| title_sort | Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects |
| topic | CYP1A1 DNA strand breakage Phenanthrene Benzo[a]pyrene Benzo[b]fluoranthene |
| topic_facet | CYP1A1 DNA strand breakage Phenanthrene Benzo[a]pyrene Benzo[b]fluoranthene |
| url | http://hdl.handle.net/10451/58891 |
| visible | 1 |