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PLoS One. 2015 Feb 6;10(2):e0117491. doi: 10.1371/journal.pone.0117491. eCollection 2015.

Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

Author information

1
Department of Dermatology, Sydney Cancer Centre, Bosch Institute, University of Sydney at Royal Prince Alfred Hospital, Camperdown, Sydney.
2
Department of Dermatology, Sydney Cancer Centre, Bosch Institute, University of Sydney at Royal Prince Alfred Hospital, Camperdown, Sydney; Melanoma Institute Australia, North Sydney, Australia.

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.

PMID:
25658450
PMCID:
PMC4319842
DOI:
10.1371/journal.pone.0117491
[Indexed for MEDLINE]
Free PMC Article

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