Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult

Detalhes bibliográficos
Autor(a) principal: Martins, Marta
Data de Publicação: 2018
Outros Autores: Silva, Ana, Costa, Maria H., Miguel, Célia, Costa, Pedro M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://doi.org/10.1038/s41598-018-21975-w
Resumo: The authors acknowledge the Portuguese Foundation for Science and Technology for the grant SFRH/BPD/109734/2015 (MM) and IF/00265/2015 (PMC) and to MARE through the strategic programme UID/MAR/04292/2013 plus UCIBIO, which is financed by FCT/MEC UID/Multi/04378/2013. The authors acknowledge Lara Carvalho, from the Fish Facility Manager - Instituto de Medicina Molecular da Faculdade de Medicina da Universidade de Lisboa, for the zebrafish tested in the present study.
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spelling Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insultGenotoxicityComet AssayNuclear abnormalitiesGeneralThe authors acknowledge the Portuguese Foundation for Science and Technology for the grant SFRH/BPD/109734/2015 (MM) and IF/00265/2015 (PMC) and to MARE through the strategic programme UID/MAR/04292/2013 plus UCIBIO, which is financed by FCT/MEC UID/Multi/04378/2013. The authors acknowledge Lara Carvalho, from the Fish Facility Manager - Instituto de Medicina Molecular da Faculdade de Medicina da Universidade de Lisboa, for the zebrafish tested in the present study.Addressing the risk of mixed carcinogens in vivo under environmentally-realistic scenarios is still a challenge. Searching for adequate biomarkers of exposure requires understanding molecular pathways and their connection with neoplasia-related benchmark pathologies. Subjecting the zebrafish model to realistic concentrations of two genotoxicants and carcinogens, cadmium and benzo[a]pyrene, isolated and combined, yielded low levels of DNA damage. Altogether, the organisms' mechanisms of DNA repair, oxidative stress and phases I and II were not overwhelmed after two weeks of treatment. Still, transcriptional responses related to detoxification (epoxide hydrolase and UDP-glucuronosyltransferase) were higher in animals subjected to the combination treatment, inclusively following depuration. Nonetheless, inflammation and formation of hyperplasic foci in fish epithelia were more severe in animals exposed to the combined substances, showing slower recovery during depuration. Additionally, the combination treatment yielded unexpected increased expression of a ras-family oncogene homologue after depuration, with evidence for increased tp53 counter-response in the same period. The findings indicate that oncogene expression, cell proliferation and inflammation, may not require noticeable DNA damage to occur. Furthermore, albeit absent proof for neoplasic growth, the removal of chemical insult may promote tissue recovery but does not entirely clear molecular and histopathological endpoints that are commonly associated to neoplasia.UCIBIO - Applied Molecular Biosciences UnitDCEA - Departamento de Ciências e Engenharia do AmbienteMARE - Centro de Ciências do Mar e do AmbienteBioresources 4 Sustainability (GREEN-IT)Instituto de Tecnologia Química e Biológica António Xavier (ITQB)DCV - Departamento de Ciências da VidaRUNMartins, MartaSilva, AnaCosta, Maria H.Miguel, CéliaCosta, Pedro M.2019-01-25T23:37:56Z2018-12-012018-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.1038/s41598-018-21975-weng2045-2322PURE: 3840390http://www.scopus.com/inward/record.url?scp=85042733436&partnerID=8YFLogxKhttps://doi.org/10.1038/s41598-018-21975-winfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:28:17Zoai:run.unl.pt:10362/58647Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:33:17.889862Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult
title Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult
spellingShingle Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult
Martins, Marta
Genotoxicity
Comet Assay
Nuclear abnormalities
General
title_short Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult
title_full Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult
title_fullStr Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult
title_full_unstemmed Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult
title_sort Co-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low-genotoxicity events, even after removal of insult
author Martins, Marta
author_facet Martins, Marta
Silva, Ana
Costa, Maria H.
Miguel, Célia
Costa, Pedro M.
author_role author
author2 Silva, Ana
Costa, Maria H.
Miguel, Célia
Costa, Pedro M.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv UCIBIO - Applied Molecular Biosciences Unit
DCEA - Departamento de Ciências e Engenharia do Ambiente
MARE - Centro de Ciências do Mar e do Ambiente
Bioresources 4 Sustainability (GREEN-IT)
Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
DCV - Departamento de Ciências da Vida
RUN
dc.contributor.author.fl_str_mv Martins, Marta
Silva, Ana
Costa, Maria H.
Miguel, Célia
Costa, Pedro M.
dc.subject.por.fl_str_mv Genotoxicity
Comet Assay
Nuclear abnormalities
General
topic Genotoxicity
Comet Assay
Nuclear abnormalities
General
description The authors acknowledge the Portuguese Foundation for Science and Technology for the grant SFRH/BPD/109734/2015 (MM) and IF/00265/2015 (PMC) and to MARE through the strategic programme UID/MAR/04292/2013 plus UCIBIO, which is financed by FCT/MEC UID/Multi/04378/2013. The authors acknowledge Lara Carvalho, from the Fish Facility Manager - Instituto de Medicina Molecular da Faculdade de Medicina da Universidade de Lisboa, for the zebrafish tested in the present study.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-01
2018-12-01T00:00:00Z
2019-01-25T23:37:56Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://doi.org/10.1038/s41598-018-21975-w
url https://doi.org/10.1038/s41598-018-21975-w
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2045-2322
PURE: 3840390
http://www.scopus.com/inward/record.url?scp=85042733436&partnerID=8YFLogxK
https://doi.org/10.1038/s41598-018-21975-w
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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