Abstract
Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially 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, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2) solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2′-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.
Highlights
Ultraviolet (UV) radiation is the primary carcinogen associated with skin cancer
There was no significant difference between the groups (n = 6, one way analysis of variance (ANOVA)) indicating that the interventions did not affect cell viability (Fig. 2)
Photolesion levels were significantly increased further by exposure to sodium arsenite compared to UV alone (p
Summary
Ultraviolet (UV) radiation is the primary carcinogen associated with skin cancer. In contaminated groundwater used for drinking and crop irrigation, is a significant cause of skin cancer globally. More than 150 million people in Bangladesh and West Bengal are at risk of arsenic-induced skin cancer. 21% of people from arsenic affected districts of Bangladesh were found to have dermatological signs of chronic arsenic toxicity [1]. Arsenic is present at high levels in drinking water in Cambodia and Vietnam [2], China [3] and PLOS ONE | DOI:10.1371/journal.pone.0117491. Arsenic is present at high levels in drinking water in Cambodia and Vietnam [2], China [3] and PLOS ONE | DOI:10.1371/journal.pone.0117491 February 6, 2015
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