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Title: An investigation into the mechanisms of aneuploidy induction in cultured mammalian cells
Author: Somers, A. N. A.
Awarding Body: University College of Swansea
Current Institution: Swansea University
Date of Award: 1987
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An established cytogenetic assay and a novel spindle staining technique were used to investigate the mechanisms of aneuploidy induction in cultured mammalian cells. The ability of the spindle staining assay to detect the aneugenic potential of an agent was established using 6 chemicals, some of which were known aneugenic agents, as model compounds. The technique appeared to be most sensitive to agents which exert a direct action upon the mitotic apparatus (for e.g. vincristine and taxol). The teratogen, thalidomide, did not appear to induce chromosome aneuploidy or aberrations, nor did it significantly disturb the fidelity of cell division in cultured mammalian cells. By the use of the spindle staining technique it appears that the ability of certain tumour promoters to induce aneuploidy in cultured mammalian cells is not the result of a direct action upon the mitotic apparatus. It appears to be a secondary effect of these chemicals which is related to their toxicity. The spindle staining technique may provide a very sensitive assay for the detection of potent spindle toxins (e.g. vinblastine) in complex extracts of the parent plant (C. roseus). It may provide an effective screening procedure for the identification of potentially valuable plant materials for their use as sources of anti-tumour agents. Concentrated water extracts of a raw sample appeared to exert a weak, non-reversible effect upon the mitotic spindle of cultured mammalian cells. The activity of a final drinking water sample remains uncertain. Both tobacco smoke and tobacco-related substances did not appear to have the potential to induce aneuploidy at the concentrations investigated and under the conditions employed in these studies. Finally, changes in the fidelity of cell division and in the integrity of mitotic spindle formation were detected in Syrian hamster dermal cells progressing from primary culture isolation to senesence and then to immortalization and transformation. The mechanisms of aneuploidy induction in cultured mammalian cells and the significance and possible role of aneuploidy in cell transformation and tumour development are discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available