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

2018-02-26Research article Open access
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dc.contributor.authorMartins, Marta
dc.contributor.authorSilva, Ana
dc.contributor.authorCosta, Maria H.
dc.contributor.authorMiguel, Célia
dc.contributor.authorCosta, Pedro M.
dc.date.accessioned2025-05-15T14:24:49Z
dc.date.available2025-05-15T14:24:49Z
dc.date.issued2018-02-26
dc.description.abstractAddressing 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.eng
dc.description.sponsorshipThe 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 zebrafsh tested in the present study.
dc.identifier.doi10.1038/s41598-018-21975-w
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10400.8/12885
dc.language.isoeng
dc.peerreviewedyes
dc.publisherNature
dc.relationUID/ MAR/04292/2013
dc.relation.hasversionhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85042733436&doi=10.1038%2fs41598-018-21975-w&partnerID=40&md5=d91e78e29cf2db1727c5534bb41d75f8
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAnimals
dc.subjectCarcinogens
dc.subjectEnvironmental
dc.subjectDNA Damage
dc.subjectDNA Repair
dc.subjectEpoxide Hydrolases
dc.subjectGlucuronosyltransferase
dc.subjectOxidative Stress
dc.subjectZebrafish
dc.subjectcarcinogen
dc.subjectepoxide hydrolase
dc.subjectglucuronosyltransferase
dc.subjectanimal
dc.subjectDNA damage
dc.subjectDNA repair
dc.subjectdrug effect
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectoxidative stress
dc.subjectzebra fish
dc.titleCo-exposure to environmental carcinogens in vivo induces neoplasia-related hallmarks in low genotoxicity events, even after removal of insulteng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.issue1
oaire.citation.titleScientific reports
oaire.citation.volume8
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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