Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced 
carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. 
Recent double-blinded randomized controlled Phase 2 studies in heavily 
sun-damaged individuals have shown that oral nicotinamide significantly reduces 
premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. 
Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an 
essential coenzyme in adenosine triphosphate (ATP) production. Previously, we 
showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. 
Energy-dependent DNA repair is a key determinant of cellular survival after 
exposure to DNA-damaging agents such as UV radiation. Hence, in this study we 
investigated whether nicotinamide protection from cellular energy loss 
influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and 
exposed them to low-dose solar-simulated UV (ssUV). Excision repair was 
quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased 
both the proportion of cells undergoing excision repair and the repair rate in 
each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers 
(CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by 
comet assay in keratinocytes and with immunohistochemistry in human skin. 
Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to 
be due to enhancement of DNA repair. These results show that nicotinamide 
enhances two different pathways for repair of UV-induced photolesions, 
supporting nicotinamide's potential as an inexpensive, convenient and non-toxic 
agent for skin cancer chemoprevention.