Publication
Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin
| Summary: | Bisphenol A (BPA) is one of the most widely utilized endocrine disruptors to which humans are exposed, particularity through ingestion. BPA is an aneugenic compound with a putative association to tumorigenesis. Although extensively studied in estrogen-responsive cells, information regarding its effects on cells from the upper gastrointestinal tract exposed to free/active forms of BPA are still scarce. Similarly, BPA interactions with other drugs has been neglected, although it has been suggested to has a potential role in doxorubicin (DOX) chemoresistance. This study is intended to assess potential cytotoxic and genotoxic effects of BPA, as well as its interactions with DOX, in Human epithelial type 2 cells (Hep-2) originated from a human laryngeal carcinoma and in a DNA damage responsive cell line, the human lung fibroblasts (MRC-5). Cell viability was analyzed through the resazurin assay. The G protein-coupled estrogen receptor 1 (GPER) expression was visualized by immunodetection. Genotoxicity, namely DNA damage and oxidative DNA damage, were assessed by comet assay and micronuclei induction, and mitotic disruption was evaluated cytologically by fluorescent microscopy wif DAPI staining. Cytotoxicity analysis showed that exposure to BPA per se does not affect cellular viability. Nevertheless, the genotoxic analysis showed that BPA induced an increase of DNA damage in the Hep-2 cell line and in oxidative damage in the MRC-5 cell line. An increase of micronuclei was also observed in both cell lines following BPA exposure. BPA and DOX co-exposures suggested that BPA acts as an antagonist of DOX effects in both cell lines. The interaction wif DOX appears to be cell type dependent, exhibiting a non-monotonic response curve in MRC-5 cells, a GPER expressing cell line. Our study emphasizes the need for a deeper knowledge of BPA interactions, particularly with chemotherapeutic agents, in the context of risk assessment and public health. |
|---|---|
| Main Authors: | Ramos, Carina |
| Other Authors: | Ladeira, Carina; Zeferino, Sofia; Dias, Ana; Faria, Isabel; Cristovam, Elisabete; Gomes, Manuel; Ribeiro, Edna |
| Subject: | Bisphenol A Doxorubicin Cytotoxicity Genotoxicity CA15132 hCOMET COST Action |
| Year: | 2019 |
| Country: | Portugal |
| Document type: | article |
| Access type: | restricted access |
| Associated institution: | Universidade Politécnica de Lisboa |
| Language: | English |
| Origin: | Repositório Científico da Universidade Politécnica de Lisboa |
| _version_ | 1880398429622894592 |
|---|---|
| author | Ramos, Carina |
| author2 | Ladeira, Carina Zeferino, Sofia Dias, Ana Faria, Isabel Cristovam, Elisabete Gomes, Manuel Ribeiro, Edna |
| author2_role | author author author author author author author |
| author_facet | Ramos, Carina Ladeira, Carina Zeferino, Sofia Dias, Ana Faria, Isabel Cristovam, Elisabete Gomes, Manuel Ribeiro, Edna |
| author_role | author |
| contributor_name_str_mv | RCIPL |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Ramos, Carina\"},{\"Person.name\":\"Ladeira, Carina\",\"Person.identifier.cienciaID\":\"801C-1BBA-1D9E\",\"Person.identifier.orcid\":\"0000-0001-5588-0074\",\"Person.identifier.researcherID\":\"J-2572-2012\",\"Person.identifier.scopusAuthorID\":\"36463788000\"},{\"Person.name\":\"Zeferino, Sofia\"},{\"Person.name\":\"Dias, Ana\"},{\"Person.name\":\"Faria, Isabel\"},{\"Person.name\":\"Cristovam, Elisabete\"},{\"Person.name\":\"Gomes, Manuel\"},{\"Person.name\":\"Ribeiro, Edna\",\"Person.identifier.cienciaID\":\"C414-CDF2-D35A\",\"Person.identifier.orcid\":\"0000-0003-1316-7750\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RCIPL |
| datacite.creators.creator.creatorName.fl_str_mv | Ramos, Carina Ladeira, Carina Zeferino, Sofia Dias, Ana Faria, Isabel Cristovam, Elisabete Gomes, Manuel Ribeiro, Edna |
| datacite.date.Accepted.fl_str_mv | 2019-02-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2018-12-25T19:36:24Z |
| datacite.date.embargoed.fl_str_mv | 2018-12-25T19:36:24Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| datacite.subjects.subject.fl_str_mv | Bisphenol A Doxorubicin Cytotoxicity Genotoxicity CA15132 hCOMET COST Action |
| datacite.titles.title.fl_str_mv | Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin |
| dc.contributor.none.fl_str_mv | RCIPL |
| dc.creator.none.fl_str_mv | Ramos, Carina Ladeira, Carina Zeferino, Sofia Dias, Ana Faria, Isabel Cristovam, Elisabete Gomes, Manuel Ribeiro, Edna |
| dc.date.Accepted.fl_str_mv | 2019-02-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2018-12-25T19:36:24Z |
| dc.date.embargoed.fl_str_mv | 2018-12-25T19:36:24Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10400.21/9198 |
| 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_16ec |
| dc.subject.none.fl_str_mv | Bisphenol A Doxorubicin Cytotoxicity Genotoxicity CA15132 hCOMET COST Action |
| dc.title.fl_str_mv | Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Bisphenol A (BPA) is one of the most widely utilized endocrine disruptors to which humans are exposed, particularity through ingestion. BPA is an aneugenic compound with a putative association to tumorigenesis. Although extensively studied in estrogen-responsive cells, information regarding its effects on cells from the upper gastrointestinal tract exposed to free/active forms of BPA are still scarce. Similarly, BPA interactions with other drugs has been neglected, although it has been suggested to has a potential role in doxorubicin (DOX) chemoresistance. This study is intended to assess potential cytotoxic and genotoxic effects of BPA, as well as its interactions with DOX, in Human epithelial type 2 cells (Hep-2) originated from a human laryngeal carcinoma and in a DNA damage responsive cell line, the human lung fibroblasts (MRC-5). Cell viability was analyzed through the resazurin assay. The G protein-coupled estrogen receptor 1 (GPER) expression was visualized by immunodetection. Genotoxicity, namely DNA damage and oxidative DNA damage, were assessed by comet assay and micronuclei induction, and mitotic disruption was evaluated cytologically by fluorescent microscopy wif DAPI staining. Cytotoxicity analysis showed that exposure to BPA per se does not affect cellular viability. Nevertheless, the genotoxic analysis showed that BPA induced an increase of DNA damage in the Hep-2 cell line and in oxidative damage in the MRC-5 cell line. An increase of micronuclei was also observed in both cell lines following BPA exposure. BPA and DOX co-exposures suggested that BPA acts as an antagonist of DOX effects in both cell lines. The interaction wif DOX appears to be cell type dependent, exhibiting a non-monotonic response curve in MRC-5 cells, a GPER expressing cell line. Our study emphasizes the need for a deeper knowledge of BPA interactions, particularly with chemotherapeutic agents, in the context of risk assessment and public health. |
| dirty | 0 |
| eu_rights_str_mv | restrictedAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ipl.pt/bitstreams/ff254354-a4d0-4a1a-ab15-4653a610518f/download |
| id | ripl_a1a5645b28bd5861e195a5fa928e1ca2 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10400.21/9198 |
| inst_facet_str | urn:organizationAcronym:ipl{{{_:::_}}}Universidade Politécnica de Lisboa |
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| institution | Universidade Politécnica de Lisboa |
| instname_str | Universidade Politécnica de Lisboa |
| language | eng |
| network_acronym_str | ripl |
| network_name_str | Repositório Científico da Universidade Politécnica de Lisboa |
| oai_identifier_str | oai:repositorio.ipl.pt:10400.21/9198 |
| organization_str_mv | urn:organizationAcronym:ipl |
| person_str_mv | Ramos, Carina Ladeira, Carina Ladeira, Carina https://www.ciencia-id.pt/801C-1BBA-1D9E 801C-1BBA-1D9E http://orcid.org/0000-0001-5588-0074 0000-0001-5588-0074 Zeferino, Sofia Dias, Ana Faria, Isabel Cristovam, Elisabete Gomes, Manuel Ribeiro, Edna Ribeiro, Edna https://www.ciencia-id.pt/C414-CDF2-D35A C414-CDF2-D35A http://orcid.org/0000-0003-1316-7750 0000-0003-1316-7750 |
| publishDate | 2019 |
| publisher.none.fl_str_mv | Elsevier |
| repo_facet_str | urn:repositoryAcronym:ripl{{{_:::_}}}Repositório Científico da Universidade Politécnica de Lisboa |
| reponame_str | Repositório Científico da Universidade Politécnica de Lisboa |
| repository_id_str | urn:repositoryAcronym:ripl |
| service_str_mv | urn:repositoryAcronym:ripl |
| spelling | engElsevierpt_PTBisphenol A (BPA) is one of the most widely utilized endocrine disruptors to which humans are exposed, particularity through ingestion. BPA is an aneugenic compound with a putative association to tumorigenesis. Although extensively studied in estrogen-responsive cells, information regarding its effects on cells from the upper gastrointestinal tract exposed to free/active forms of BPA are still scarce. Similarly, BPA interactions with other drugs has been neglected, although it has been suggested to has a potential role in doxorubicin (DOX) chemoresistance. This study is intended to assess potential cytotoxic and genotoxic effects of BPA, as well as its interactions with DOX, in Human epithelial type 2 cells (Hep-2) originated from a human laryngeal carcinoma and in a DNA damage responsive cell line, the human lung fibroblasts (MRC-5). Cell viability was analyzed through the resazurin assay. The G protein-coupled estrogen receptor 1 (GPER) expression was visualized by immunodetection. Genotoxicity, namely DNA damage and oxidative DNA damage, were assessed by comet assay and micronuclei induction, and mitotic disruption was evaluated cytologically by fluorescent microscopy wif DAPI staining. Cytotoxicity analysis showed that exposure to BPA per se does not affect cellular viability. Nevertheless, the genotoxic analysis showed that BPA induced an increase of DNA damage in the Hep-2 cell line and in oxidative damage in the MRC-5 cell line. An increase of micronuclei was also observed in both cell lines following BPA exposure. BPA and DOX co-exposures suggested that BPA acts as an antagonist of DOX effects in both cell lines. The interaction wif DOX appears to be cell type dependent, exhibiting a non-monotonic response curve in MRC-5 cells, a GPER expressing cell line. Our study emphasizes the need for a deeper knowledge of BPA interactions, particularly with chemotherapeutic agents, in the context of risk assessment and public health.application/pdfpt_PTCytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicinRamos, CarinaPersonalLadeira, CarinaDSpacehttp://dspace.org/items/1aef4b60-4197-436b-84ab-80d31cbaed33DSpacehttp://dspace.org/items/1aef4b60-4197-436b-84ab-80d31cbaed33LadeiraCarinaCiência IDhttps://www.ciencia-id.pt801C-1BBA-1D9EORCIDhttp://orcid.org0000-0001-5588-0074Researcher IDhttps://www.researcherid.comJ-2572-2012Scopus Author IDhttps://www.scopus.com36463788000Zeferino, SofiaDias, AnaFaria, IsabelCristovam, ElisabeteGomes, ManuelPersonalRibeiro, EdnaDSpacehttp://dspace.org/items/a571bf34-bcda-49ca-b5cb-4cdecbb3d9c7DSpacehttp://dspace.org/items/a571bf34-bcda-49ca-b5cb-4cdecbb3d9c7RibeiroEdnaCiência IDhttps://www.ciencia-id.ptC414-CDF2-D35AORCIDhttp://orcid.org0000-0003-1316-7750HostingInstitutionOrganizationalRCIPLe-mailmailto:rcaap@sp.ipl.ptrcaap@sp.ipl.ptDOIIsPartOf10.1016/j.mrgentox.2018.11.0092018-12-25T19:36:24Z2019-022019-02-01T00:00:00ZHandlehttp://hdl.handle.net/10400.21/9198http://purl.org/coar/access_right/c_16ecrestricted accessBisphenol ADoxorubicinCytotoxicityGenotoxicityCA15132 hCOMET COST Action1225860 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2019-02http://creativecommons.org/licenses/by-nc-nd/4.0/http://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.ipl.pt/bitstreams/ff254354-a4d0-4a1a-ab15-4653a610518f/downloadMutation Research - Genetic Toxicology and Environmental Mutagenesis8382836 |
| spellingShingle | Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin Ramos, Carina Bisphenol A Doxorubicin Cytotoxicity Genotoxicity CA15132 hCOMET COST Action |
| status | SINGLETON |
| subject.fl_str_mv | Bisphenol A Doxorubicin Cytotoxicity Genotoxicity CA15132 hCOMET COST Action |
| title | Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin |
| title_full | Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin |
| title_fullStr | Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin |
| title_full_unstemmed | Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin |
| title_short | Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin |
| title_sort | Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin |
| topic | Bisphenol A Doxorubicin Cytotoxicity Genotoxicity CA15132 hCOMET COST Action |
| topic_facet | Bisphenol A Doxorubicin Cytotoxicity Genotoxicity CA15132 hCOMET COST Action |
| url | http://hdl.handle.net/10400.21/9198 |
| visible | 1 |
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