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Title: Investigations into chromosome-specific susceptibilities to aneuploidy
Author: Bourner, R. D. P.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 1998
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The study of chemically induced aneuploidy in mammalian cells is generally conducted by the selection of one or a few chromosomes to serve as an index for total aneuploidy within the test-system used. However, a large body of evidence exists to suggest that not all chromosomes undergo non-disjunction and/or chromosome loss at the same frequency. Hence the behaviour of one selected chromosome may not be adequately parallel total cell events, whether experimentally induced or spontaneously arising. A review of the evidence for chromosomal differences in susceptibility to aneuploidy was made, and a number of chromosomal properties which could conceivably account for this difference were identified. Frequencies of experimentally derived mitotic aneuploidy and reported spontaneous meiotic aneuploidy for different chromosomes were then investigated in an attempt to identify the underlying mechanisms responsible for individual chromosome susceptibility. An improved protocol for metaphase preparation is proposed to reduce the influence of artefactual chromosomal loss in cultured mammalian cells. The induction of aneuploidy by the model aneugens colcemid and griseofulvin was investigated in the monochromosomal human/mouse hybrid cell line, R3-5, and in human lymphocytes exposed in vitro. Application of FISH technology permitted the identification of specific chromosome pairs, and the characterisation involvement in observed aneuploidy demonstrated significant heterogeneity in response, and this was correlated to putative causal factors. A FISH probe suitable for interphase analysis in the hybrid was constructed and optimised for use. The suitability of FISH methodology in assessing chemically induced aneuploidy in in vitro systems was demonstrated. Low doses of aneugen exposure were investigated and a threshold effect on quantified response was demonstrated for both aneugens. Nondisjunction appears to be the predominant form of aberration at low doses, reaching significant at doses that are ineffective in the micronucleus assay.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available