Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.564207
Title: Investigation of ultraviolet radiation-induced DNA damage and repair in human skin cells
Author: Karbaschi, Mahsa
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2012
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Abstract:
UVR, by initiating the DNA damage, can lead to mutagenesis and is regarded as the prime cause of most skin cancers. Cyclobutane pyrimidine dimers (CPD) are an important form of DNA damage induced by both UVA and UVB and removed by nucleotide excision repair. Classically, the repair of CPDs is reported to be a lengthy process. The persistence of CPDs, compared to other forms of DNA damage, is understood to be a major contributory factor to their mutagenicity. In this study, using the T4endonucleaseV-modified comet assay for CPDs, the standard slow repair of UVB-induced CPDs were confirmed, but repair of UVA-induced CPDs was more rapid in human keratinocytes and fibroblasts. A rapid initial repair of CPDs over the first 6 h post-irradiation, following either UVA or UVB treatments was noted in both cell types, but whilst this slowed significantly in the UVB-irradiated cells, it continued to be rapid in the UVA-treated cells with levels approaching baseline within 36 h. Up-regulation to the baseline level of key genes associated with nucleotide excision repair in UVA-irradiated cells, compared to down regulation of the same genes in UVB-irradiated cells was noted. There were no significant differences in cell viability between the two treatments over the first 6 h post-irradiation but, at 24 h post-irradiation, viability had decreased significantly in the UVB-irradiated cells only. These data suggest that for at least the first six hours following UVB irradiation, the majority of cells are viable and capable of repair, after that time increasing numbers of cells enter apoptosis, and cease to repair the damage. Discrimination of dead/dying cells from viable cells in any repair assay is a possible element of artefact in determining the repair kinetics of CPDs. This would contribute to the apparent slow repair of CPDs widely reported in the literature.
Supervisor: Cooke, Marcus; Evans, Mark Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.564207  DOI: Not available
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