Thenet, Delphine Julie (2012) An investigation into the use of 3D microscopy for the study of radiation-induced chromosome aberrations and nuclear architecture. (PhD thesis), Kingston University, .
Abstract
Cellular exposure to ionising radiation (IR) generates chromosome aberrations (CA) that in turn lead to gene mutation and cell death. Although radiation-induced CA are known to result from the misrepair or lack of repair of DNA damage, the exact details of the conversion of such damage to CA remains unclear especially with regard to those CA that involve two or more chromosomes. In interphase cells, chromosomes occupy discrete territories that under specific conditions appear conserved within any cell type. Territories appear to have both structural and functional importance and their position within the nucleus is apparently dynamic and changes during the cell cycle. The existence of territories suggests that in three dimensions, chromosomes differ in their spatial relationship. The aims of this thesis were to develop methods for 3D analysis and visualisation of chromosome territories in human primary fibroblasts and bladder carcinoma (RTl12) cell nuclei to enable chromosome characterisation. The relationship between CA formation following irradiation and nuclear architecture was investigated using fluorescence in situ hybridization and confocal microscopy in the two cell lines. Analysis and visualisation methods were developed and applied in order to assess chromosome properties in relation to the nucleus. Chromosome 1 and chromosome 2 territories were successfully imaged in non-irradiated and irradiated cell nuclei. 3D analysis and visualisation enabled the identification and quantification of complete and fragmented chromosomes territories. The methods developed may thus help to elucidate the mechanisms of radiation induced chromosome aberrations and hence have application in cancer cell biology.
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