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Nicotinamide Attenuates UV-Induced Stress Damage in Human Primary Keratinocytes from Cancerization Fields

Published:October 22, 2021DOI:https://doi.org/10.1016/j.jid.2021.10.012
      UVB radiation directly damages DNA, increases ROS and nitric oxide (NO) release, and promotes inflammation leading to genomic instability and cell death. Nicotinamide (NAM) is the precursor of NAM adenine dinucleotide, 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 and those isolated from field cancerization (i.e., field cancerization human primary keratinocytes [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 human epidermal keratinocytes. Cells were treated for 18, 24, and 48 hours with NAM (5, 25, and 50 μM, respectively) before UVB irradiation. FC-HPK showed four-fold higher basal ROS levels than normal human epidermal keratinocytes; NAM downregulated ROS production only in irradiated FC-HPKs, which showed a greater sensibility to UV rays. UV exposure increased OGG1, inducible nitric oxide synthase, and IL-1β expression, an effect counteracted by NAM pretreatment. Intracellular nitric oxide production and DNA damages were inhibited by NAM exposure before irradiation. Collectively, our findings indicate that pretreatment with 25 μM NAM 24 hours before UVB irradiation effectively prevents oxidative stress formation, DNA damage, and inflammation in both normal human epidermal keratinocytes and FC-HPKs.

      Graphical abstract

      Abbreviations:

      8-oxoG (8-oxo-7,8-dihydro-2′-deoxyguanosine), FC-HPK (field cancerization human primary keratinocyte), HPK (human primary keratinocyte), iNOS (inducible nitric oxide synthase), KC (keratinocyte), NAM (nicotinamide), NHEK (normal human epidermal keratinocyte), NMSC (nonmelanoma skin cancer), NO (nitric oxide)
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