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

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dc.contributor.advisor Van Pelt, Frank en
dc.contributor.advisor O'Halloran, John en Dörr, Barbara Valentina 2015-04-30T13:34:22Z 2015-04-30T13:34:22Z 2014 2014
dc.identifier.citation Dörr, B. V. 2014. Investigation of the genotoxic potential of the marine biotoxins okadaic acid and azaspiracids. PhD Thesis, University College Cork. en
dc.identifier.endpage 145
dc.description.abstract The 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.sponsorship Higher Education Authority (HEA PRTLI4) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Barbara Valentina Dörr en
dc.rights.uri en
dc.subject Okadaic acid en
dc.subject Azaspiracid en
dc.subject Genotoxicity en
dc.subject Apoptosis en
dc.subject Marine biotoxins en
dc.title Investigation of the genotoxic potential of the marine biotoxins okadaic acid and azaspiracids en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Science) en
dc.internal.availability Full text available en No embargo required en
dc.description.version Accepted Version
dc.contributor.funder Higher Education Authority en
dc.description.status Not peer reviewed en Pharmacology and Therapeutics en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Not applicable en
dc.internal.conferring Autumn Conferring 2014

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© 2014, Barbara Valentina Dörr Except where otherwise noted, this item's license is described as © 2014, Barbara Valentina Dörr
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