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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arsenites / pharmacology*
  • Cell Line
  • DNA Damage / drug effects*
  • DNA Damage / radiation effects
  • DNA Repair / drug effects*
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / radiation effects
  • Niacinamide / pharmacology*
  • Skin / drug effects*
  • Skin / radiation effects
  • Sodium Compounds / pharmacology*
  • Ultraviolet Rays*
  • Wound Healing / drug effects

Substances

  • Arsenites
  • Sodium Compounds
  • Niacinamide
  • sodium arsenite

Grant support

The project was funded by the Australasian College of Dermatologists Scientific Research Fund (DD) the Sydney Medical School Foundation (BT), Cancer Council New South Wales and the National Health and Medical Research Council of Australia (DD, GH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.