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Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicin

2019-02Journal article Restricted access
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dc.contributor.authorRamos, Carina
dc.contributor.authorLadeira, Carina
dc.contributor.authorZeferino, Sofia
dc.contributor.authorDias, Ana
dc.contributor.authorFaria, Isabel
dc.contributor.authorCristovam, Elisabete
dc.contributor.authorGomes, Manuel
dc.contributor.authorRibeiro, Edna
dc.date.accessioned2018-12-25T19:36:24Z
dc.date.available2018-12-25T19:36:24Z
dc.date.issued2019-02
dc.description.abstractBisphenol 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRamos C, Ladeira C, Zeferino S, Dias A, Faria I, Ribeiro E, et al. Cytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions wif doxorubicin. Mutat Res Genet Toxicol Environ Mutagen. 2019;838(February):28-36.pt_PT
dc.identifier.doi10.1016/j.mrgentox.2018.11.009pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/9198
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationCA15132 hCOMET COST Action – European Cooperation in Science and Technologypt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S138357181830202X?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectBisphenol Apt_PT
dc.subjectDoxorubicinpt_PT
dc.subjectCytotoxicitypt_PT
dc.subjectGenotoxicitypt_PT
dc.subjectCA15132 hCOMET COST Actionpt_PT
dc.titleCytotoxic and genotoxic effects of environmental relevant concentrations of bisphenol A and interactions with doxorubicinpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage36pt_PT
oaire.citation.startPage28pt_PT
oaire.citation.titleMutation Research - Genetic Toxicology and Environmental Mutagenesispt_PT
oaire.citation.volume838pt_PT
person.familyNameLadeira
person.familyNameRibeiro
person.givenNameCarina
person.givenNameEdna
person.identifier144237
person.identifier.ciencia-id801C-1BBA-1D9E
person.identifier.ciencia-idC414-CDF2-D35A
person.identifier.orcid0000-0001-5588-0074
person.identifier.orcid0000-0003-1316-7750
person.identifier.ridJ-2572-2012
person.identifier.scopus-author-id36463788000
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication1aef4b60-4197-436b-84ab-80d31cbaed33
relation.isAuthorOfPublicationa571bf34-bcda-49ca-b5cb-4cdecbb3d9c7
relation.isAuthorOfPublication.latestForDiscoverya571bf34-bcda-49ca-b5cb-4cdecbb3d9c7

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