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NICOTINAMIDE EXERTS A PROTECTIVE EFFECT FROM UV-INDUCED STRESS DAMAGES ON HUMAN PRIMARY KERATINOCYTES FROM CANCERIZATION FIELD.

Published:October 22, 2021DOI:https://doi.org/10.1016/j.jid.2021.10.012

      Abstract

      Ultraviolet B (UVB) radiation directly damages DNA, increases reactive oxygen species (ROS) and nitric oxide (NO) release, and promotes inflammation leading to genomic instability and cell death. Nicotinamide (NAM) is the precursor of NAD, essential for cell energy production and DNA damage repair. NAM protects HaCat cells from UV-induced impairment; however, little is known about its effects on human primary keratinocytes (HPKs) and those isolated from field cancerization (FC-HPKs). We examined the role of NAM against UV-induced oxidative stress damages in FC-HPKs, isolated from precancerous lesions and skin cancers, and in normal epidermal keratinocytes (NHEK). Cells were treated for 18, 24, and 48 hours with NAM (5, 25, and 50 μM) before UVB irradiation. FC-HPK showed 4-fold higher basal ROS levels, comparing with NHEK; NAM downregulated ROS production only in irradiated FC-HPK, that showed a greater sensibility to UV rays. UV exposure increased OGG1, iNOS and IL-1β expression, an effect counteracted by NAM pre-treatment. Intracellular NO production and DNA damages were inhibited by NAM exposure before irradiation. Collectively, our findings indicate that pre-treatment with 25 μM NAM 24h before UVB irradiation effectively prevents oxidative stress formation, DNA damages, and inflammation in both NHEKs and FC-HPKs.

      Graphical abstract

      Key words

      ABBREVIATIONS:

      ultraviolet ((UV)), reactive oxygen species ((ROS)), nitric oxide ((NO)), nicotinamide ((NAM)), human primary keratinocytes ((HPKs)), field cancerization human primary keratinocytes ((FC-HPKs)), Non-Melanoma Skin Cancers ((NMSCs)), 8-oxoguanine DNA glycosylase 1 ((OGG1)), inducible nitric oxide synthase ((iNOS)), cyclobutane pyrimidine dimers ((CPDs)), superoxide dismutase 1 ((SOD1)), 8-oxo-7,8-dihydro-2’-deoxyguanosine ((8oxoG)), DNA repair enzyme poly-ADP-ribose polymerase ((PARP)), cutaneous melanoma ((CM)), actinic keratoses ((AKs)), BCC ((basal cell carcinoma)), SCC ((squamous cell carcinoma))
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