Nicotinamide Enhances Repair of Arsenic and Ultraviolet Radiation-Induced DNA Damage in HaCaT Keratinocytes and Ex Vivo Human Skin

被引：37
作者：
Thompson, Benjamin C. [1 ]
Halliday, Gary M. [1 ]
Damian, Diona L. [1 ,2 ]
机构：
[1] Univ Sydney, Royal Prince Alfred Hosp, Bosch Inst, Sydney Canc Ctr,Dept Dermatol, Sydney, NSW 2006, Australia
[2] Melanoma Inst Australia, Sydney, NSW, Australia
来源：
PLOS ONE | 2015年 / 10卷 / 02期
基金：
英国医学研究理事会;
关键词：
INDUCED IMMUNOSUPPRESSION; DRINKING-WATER; NITRIC-OXIDE; WEST-BENGAL; GENERATION; APOPTOSIS; CELLS; METABOLISM; SURVIVAL; PROTEIN;
D O I：
10.1371/journal.pone.0117491
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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 2 mu M sodium arsenite and low dose (2J/cm(2)) 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.
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页数：13
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