|Title:||The Role of Nicotinamide in DNA Repair and Prevention of Non-melanoma Skin Cancer|
|Keywords:||Discipline of Dermatology.|
|Publisher:||University of Sydney.|
Faculty of Medicine.
Discipline of Dermatology.
|Abstract:||Ultraviolet radiation (UVR) from sunlight is the main environmental risk factor in the development of non-melanoma skin cancer (NMSC). Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) make up almost all NMSC. Actinic keratosis (AK), SCC precursor lesion, is often used as surrogate endpoint biomarker in skin cancer chemoprevention trial. UVR damages DNA directly, resulting in formation of cyclobutane pyrimidine dimers (CPDs), and also indirectly by inducing oxidative photolesion 8-oxo-7,8-dihydro-2’-deoxyguanine (8-oxodG). This project examines the role of nicotinamide, an amide form of vitamin B3, in DNA repair and prevention of NMSC. The effect of nicotinamide on nuclear DNA repair in solar-simulated (ss)UV-irradiated HaCaT keratinocytes was assessed using unscheduled DNA synthesis (UDS). Nicotinamide significantly increased both the rates of UDS in each cell and the percentage of cells showing UDS. Using comet assay to measure photolesions in HaCaTs, nicotinamide was shown to enhance repair of ssUV-induced CPDs and 8-oxodG. Immunostaining of whole human skin using antibody specific to CPDs and 8-oxodG allows localization of these photolesions in human skin. Nicotinamide significantly enhanced repair of both CPD and 8-oxodG in ssUV-irradiated whole human skin. Phase II double-blinded randomized placebo controlled clinical trials on healthy subjects with an average of more than 30 AKs each were conducted and showed that nicotinamide given at doses of 500mg twice daily (study 1) and 500mg once daily (study 2) significantly reduced AKs by 35% and 29% respectively, relative to placebo within 4 months. Nicotinamide is a promising agent for skin cancer chemoprevention|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (Open Access)|
|SURJANA Devita - Final thesis.pdf||Final thesis||13.38 MB||Adobe PDF|
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