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Title: Cytotoxicity and genotoxicity of urban particulate matter in DNA repair proficient and deficient mammalian cells
Author: Dumax-Vorzet, Audrey
ISNI:       0000 0004 2719 5565
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2010
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Air pollution (especially airborne particulate matter (PM)) can have serious effects on human health. PM exposure can increase cardiovascular and pulmonary complaints and lung cancer. These health effects reflect alterations in cellular function possibly due to damage in DNA caused by PM. A number of specialised pathways exist in mammalian cells to repair and I or by-pass different types of DNA damage. Base excision repair deals with oxidative DNA lesions which are recognised by Oggl, Nthl and Neill DNA glycosylases. The aim of this study is to investigate the role of different DNA repair proteins (including DNA glycosylases) in the protection of cellular DNA against PM-induced damage. To do so, the expression level of the proteins of interest was reduced in mouse cells and the level of cell death and DNA damage in these cells was studied and compared with unmodified I control cells. The oxidative capacity of PM was investigated to try and understand the mechanism involved in cellular toxicity. Different PM samples were used in this study: PM collected in. Manchester during the summer and winter, diesel exhaust dust from a race car engine and standard urban dust from NIST. All the PM samples could catalyse the production of oxygen radicals in the absence of cells, but DEP only could generate oxygen radicals inside cells. All the PM samples caused cell death and DNA damage, but to a different extent. Urban dust caused more cells death and DNA damage than the other PM samples. Nthl and Oggl protect mammalian cells against PM-induced cell death while Neill did not have any effect. DNA polymerase K may also have a small role in the preservation of cell viability following PM exposure. Urban dust and DEP caused a higher level of DNA damage in Nthl and Oggl deficient cells than in control cells. Neill deficiency decreased the level of DNA damage following DEP exposure compared to control cells. This study showed that DNA glycosylases are important for the protection of mouse cells against PM-induced DNA damage and cell death. These results indicate that the activity of DNA repair proteins may help predict individual sensitivity to PM- induced health effects in exposed subjects.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available