Investigation of the genotoxic potential of the marine biotoxins okadaic acid and azaspiracids

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dc.check.embargoformatNot applicableen
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dc.contributor.advisorVan Pelt, Franken
dc.contributor.advisorO'Halloran, Johnen
dc.contributor.authorDörr, Barbara Valentina
dc.contributor.funderHigher Education Authorityen
dc.date.accessioned2015-04-30T13:34:22Z
dc.date.available2015-04-30T13:34:22Z
dc.date.issued2014
dc.date.submitted2014
dc.description.abstractThe present study investigated the genotoxic potential of the marine biotoxins okadaic acid (OA) and azaspiracids (AZAs). Harmful algae blooms (HABs) are an increasing global problem with implications for the ecosystem, economy and human health. Most data available on human intoxication are based on acute toxicity. To date, limited data has been published on possible long term effects, carcinogenicity and genotoxicity. To investigate genotoxicity in the present study, DNA fragmentation was detected using the COMET assay. In contrast to most other available studies, two further endpoints were included. The Trypan Blue Exclusion assay was used to provide information on possible cytotoxicity and assess the right concentration range. Flow cytometer analysis was included to detect the possible involvement of apoptotic processes. In house background data for all endpoints were established using positive controls. Three different cell lines, Jurkat T cells, CaCo-2 cells and HepG-2 cells, representing the main target organs, were exposed to OA and AZA1-3 at different concentrations and exposure times. Data obtained from the COMET assay showed an increase in DNA fragmentation for all phycotoxins, indicating a modest genotoxic effect. However, the data obtained from the Trypan Blue Exclusion assay showed a clear reduction in cell viability and cell number, indicating the involvement of cytotoxic and/or apoptotic processes. This is supported by data obtained by flow cytometer analysis. All phycotoxins investigated showed signs of early/late apoptosis. Therefore, the combined observations made in the present study indicate that OA and AZA1-3 are not genotoxic per se. Apoptotic processes appear to make a major contribution to the observed DNA fragmentation. The information obtained in this study stresses the importance of inclusion of additional endpoints and appropriate positive controls in genotoxicity studies. Furthermore, these data can assist in future considerations on risk assessment, especially regarding repeated exposure and exposure at sub-clinical doses.en
dc.description.sponsorshipHigher Education Authority (HEA PRTLI4)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDörr, B. V. 2014. Investigation of the genotoxic potential of the marine biotoxins okadaic acid and azaspiracids. PhD Thesis, University College Cork.en
dc.identifier.endpage145
dc.identifier.urihttps://hdl.handle.net/10468/1788
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2014, Barbara Valentina Dörren
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectOkadaic aciden
dc.subjectAzaspiraciden
dc.subjectGenotoxicityen
dc.subjectApoptosisen
dc.subjectMarine biotoxinsen
dc.thesis.opt-outfalse
dc.titleInvestigation of the genotoxic potential of the marine biotoxins okadaic acid and azaspiracidsen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorf.vanpelt@ucc.ie
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