Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636657
Title: Development and application of in vitro micronucleus test : the quest for a suitable cell type
Author: Williamson, J.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 2000
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Abstract:
To prevent unnecessary human exposure to aneugens, regulatory agencies are beginning to suggest screening for induced aneuploidy be undertaken. There are two mechanisms by which aneuploidy may arise, non-disjunction and chromosome loss. To fully assess the aneugenic potential of a compound a test that can detect both should be employed. At present, the cytokinesis-blocked micronucleus assay is the only assay that can, when coupled with the appropriate molecular probing technologies, detect both mechanisms. The use of the in vitro micronucleus assay to detect aneuploidy is a relatively recent advance and as such regulatory bodies are yet to include the test in the recommended guidelines for testing. In consequence, in recent years great efforts to validate the assay have been made and the work presented here was performed to this end. In this study, the in vitro micronucleus assay in conjunction with fluorescence labelling techniques, was assessed to determine the assay's ability to detect induced aneuploidy. An important part of this investigation focused upon the cell type to be used. Ideally, to detect non-disjunction a karyotypically stable cell type should be employed. A such, the primary humans cell types, whole blood lymphocytes, extended-term (ET) lymphocytes, isolated lymphocytes and fibroblasts were investigated. In principle, the ET lymphocytes, represented the most suitable cell type. However, the ET system for testing aneugens revealed unexpected problems that required a series of further investigations which illustrated the significance of pH in cell culture division fidelity. Finally, studies were also undertaken to determine the role of metabolism in aneugen activity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.636657  DOI: Not available
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