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Title: Assessment of genotoxic potential using cytokinesis blocked micronucleus assay
Author: Kayani, M. A.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 2000
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Importance and effects of aneuploidy has long been debated. Aneuploidy is now considered sufficiently important to be included in the routine testing of chemicals and radiations. Aneuploidy may arise by at least two mechanisms, chromosome loss and non-disjunction. Over the past few years, the Cytokinesis Blocked Micronucleus (CBMN) technique has evolved into a robust assay for the detection of aneuploidy induction. At present, it is the only assay, which can detect both chromosome loss and non-disjunction reliably when coupled with appropriate molecular probing techniques. The present study aimed at the assessment of genotoxic potential of three major groups of chemicals using CBMN assay, applied in conjunction with kinetochore labelling and Fluorescence in situ Hybridization. In first part, the aneuploidy induction by ethanol and acetaldehyde was studied. The results focussed on the ability of ethanol and acetaldehyde to produce genotoxic effects produced by aneugenic and clastogenic mechanisms respectively. The results from the present study suggest that ethanol is an aneugen itself and the ability of ethanol to produce mutagenic effects depends on the ability of specific cells or tissue to absorb and metabolise ethanol efficiently. In second part, the aneuploidy induction by three groups of hormones was studied using CBMN assay coupled with Fluorescence in situ Hybridization. The results from the present study suggest that 17-β Oestradiol, Diethylstilboesterol, Progesterone and Testosterone are genotoxic and induce aneuploidy by non-disjunctional mechanism. In the third part of this thesis, experiments were carried out to study the toxic consequence of xenobiotic-diacylglycerols, which have been ignored in the past many years. The results from this study, for the first time, have shown that xenobiotic diacylglycerols can induce aneuploidy and this may provide a link between environmental exposure and hyperproliferative diseases in which disruption of cell cycle is a critical factor. At least one xenobiotic-DG (Ibuprofen-DG) was found to induce aneuploidy in vitro in mammalian cultures. Finally, the results from this present study shows the usefulness, reliability and sensitivity of CBMN assay which can now be routinely used for the assessment of genotoxic potential of different factors.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available