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Cytotoxic responses of the anticancer drug cyclophosphamide in the mussel Mytilus galloprovincialis and comparative sensitivity with human cells lines

dc.contributor.authorFernandes, Elna
dc.contributor.authorFonseca, Tainá
dc.contributor.authorCarriço, Tania
dc.contributor.authorMestre, Nélia
dc.contributor.authorTavares, Alvaro
dc.contributor.authorBebianno, Maria
dc.date.accessioned2021-06-18T16:25:44Z
dc.date.available2021-06-18T16:25:44Z
dc.date.issued2020-12
dc.description.abstractthe rise of cancer cases worldwide led to an increase in production and consumption of anticancer drugs, that ultimately end up in the marine environment and are accumulated in aquatic organisms. Cyclophosphamide (CP) is a cytotoxic alkylating agent frequently prescribed in cancer treatments. This study assess ecotoxicological effects of CP on mussels Mytilus galloprovincialis, through in vivo and ex vivo approaches and compares the sensitivity of mussel haemocytes with well-established human cell lines (RPE and HeLa). Mussels were exposed in vivo to CP (1000 ng L-1) and several biomarkers analysed in gills and digestive glands namely neurotoxicity (AChE activity), oxidative stress (GPx activity), biotransformation (GST activity), lipid peroxidation (LPO) and apoptosis (caspase activity), whereas genotoxicity was determined in mussels' haemocytes. Cytotoxicity was also assessed in haemocytes (in vivo and ex vivo) and human cell lines (in vitro) exposed to a range of CP concentrations (50, 100, 250, 500 and 1000 ng L-1) over 24 h, via neutral red assay. In in vivo exposure, detoxification of CP did not efficiently occur in the gills while in digestive glands GPx and GST activities were induced, jointly with a decrease in lipid peroxidation, indicating a potential outcome of the protective antioxidant mechanisms, whereas no apoptosis was noted. Moreover, cytotoxicity and DNA damage were detected in haemocytes. the ex vivo exposure haemocytes to CP caused cytotoxicity (from 100 ng L-1), whereas no effects occurred in human cell lines. This suggests that, at relevant environmental concentrations, CP cause subtle and irreversible impacts on M. galloprovincialis. (C) 2020 Elsevier Ltd. All rights reserved.
dc.description.sponsorshipFCTPortuguese Foundation for Science and TechnologyEuropean Commission [UID//00350/2020]
dc.description.sponsorshipproject EMERGEMIX [PTDC/BIA-BMA/30922/2017]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/j.chemosphere.2020.127678
dc.identifier.issn0045-6535
dc.identifier.urihttp://hdl.handle.net/10400.1/15660
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.subjectAnticancer drugs
dc.subjectCyclophosphamide
dc.subjectToxicity
dc.subjectMytilus galloprovincialis
dc.subjectHuman cells
dc.subject.otherEnvironmental Sciences & Ecology
dc.titleCytotoxic responses of the anticancer drug cyclophosphamide in the mussel Mytilus galloprovincialis and comparative sensitivity with human cells lines
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/152148/PT
oaire.citation.startPage127678
oaire.citation.titleChemosphere
oaire.citation.volume261
oaire.fundingStream9471 - RIDTI
person.familyNameGARCIA DA FONSECA
person.familyNameMestre
person.familyNameBebianno
person.givenNameTAINÁ
person.givenNameNélia
person.givenNameMaria
person.identifier195864
person.identifier.ciencia-idCC10-4E47-B6DD
person.identifier.ciencia-idD71D-759D-F6FC
person.identifier.ciencia-id2B11-46AC-B94B
person.identifier.orcid0000-0001-6871-9984
person.identifier.orcid0000-0003-1492-8566
person.identifier.ridC-1943-2009
person.identifier.scopus-author-id35237689600
person.identifier.scopus-author-id7004152715
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
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