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

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.

Canon Ulick Bourke: cultural nationalism, popular politics and the Knock apparition

Accounts of the Knock Apparition, academic and devotional, always start by relating that the Virgin Mary, St Joseph, and St John the Evangelist appeared to fifteen people on a rainy Thursday evening at the south gable of Knock chapel, Co. Mayo, on 21 August 1879. They usually mention that the Land War was in progress. Despite the fact Knock supposedly receives one and a half million visitors a year, until three decades ago no scholar had examined accounts of the apparition. Recent work has sought to define the Knock Apparition in light of the Land War, the ‘devotional revolution’, which took place in Irish Catholicism in the quarter century prior to the apparition, and the influence of the parish priest, Archdeacon Bartholomew Cavanagh. This thesis acknowledges these factors, but contends that the single greatest force in shaping accounts of the apparition was Canon Ulick Joseph Bourke, one of the three priests on the commission of investigation into Knock. Furthermore, this thesis proves that Bourke’s role as a central figure in influencing the later Gaelic revival has been overlooked by scholars of cultural nationalism. By examining Bourke’s cultural nationalism and views on antiquity and language, as well as his politics and reaction to the Land War, this thesis argues that Bourke sought to create an orthodox version of the apparition which could be reconciled to his views on Irish Catholic identity, while serving as a bulwark against threats to the temporal power of the clergy. In addition to influencing accounts of the apparition through his role in interviewing the witnesses and recording their testimony, Bourke further shaped the narrative of the apparition by controlling its dissemination, to the extent that all accounts of Knock are based on a text largely created by him.