Oral Presentation 6th Australian Health and Medical Research Congress 2012

Effect of Nicotinamide on UV and Arsenic induced DNA damage. (#136)

B C Thompson 1 , D L Damian 1 , G M Halliday 1
  1. University of Sydney, NSW, Australia

DNA damage is a central component of skin carcinogenesis. Whilst ultraviolet (UV) radiation is the prime cause of skin cancer, chemical carcinogens such as arsenic also play an important role in skin cancer development in exposed populations. Arsenic is present in water obtained from tube wells in Bangladesh and West Bengal. Affected populations, estimated to be in excess of 42 million people, show greatly elevated skin cancer incidence.  The risk of arsenic-induced skin cancers can remain elevated many years after cessation of arsenic exposure. Arsenic and UV act as skin cancer co-carcinogens in mouse models and have been shown to cause oxidative DNA damage synergistically. Nicotinamide (vitamin B3) is a safe, widely available and affordable vitamin that has been shown to replenish cellular ATP after UV exposure and to enhance DNA repair. To determine its effects on repair of DNA damage, human HaCaT keratinocytes were incubated with nicotinamide and arsenic, before exposure to 2J/cm2 of solar simulated UV radiation. Following UV exposure, cells were allowed to undergo DNA repair for 15, 30, 45 and 75 minutes before being fixed in ice cold methanol and acetone. Detection of 8-Oxo-2'-deoxyguanosine (8oxoG), reflecting oxidative DNA damage, was determined by immunoflouresence. Sodium arsenite significantly increased levels of 8oxoG in irradiated but not in unirradiated keratinocytes (p<0.01 by repeated measures ANOVA). Treatment with nicotinamide significantly decreased levels of 8oxoG over the time period studied in irradiated cells treated with both UV alone and in those treated with UV plus arsenic (p<0.05). Nicotinamide significantly reduced the oxidative DNA damage caused by both UV exposure and arsenic, likely by boosting rates of DNA repair. It is a promising agent for skin cancer chemoprevention in populations at risk of arsenic-induced skin cancer.