Effect of nicotinamide on arsenic and UV induced DNA damage

Abstract

Malignant melanoma and arsenic-induced skin cancer pose significant global health problems. In areas with arsenic contamination of water sources, such as Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin. This thesis investigated whether nicotinamide affected DNA repair in HaCaT keratinocytes following exposure to UV and sodium arsenite and also in melanocytes following exposure to UV. HaCaT keratinocytes and ex vivo human skin were exposed to 2 µM sodium arsenite and low dose (2 J/cm2) UV, with and without nicotinamide supplementation. Primary melanocytes were exposed to UV alone, with or without nicotinamide. DNA photolesions in the form of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8oxoG) and cyclobutane pyrimidine dimers were subsequently detected by immunofluorescence. Arsenic exposure significantly increased levels of 8oxoG in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes, primary melanocytes and in ex vivo human skin. These results demonstrate a reduction of two photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of skin cancer.