Gp91phox‐derived Reactive Oxygen Species/Urocortin 2/Corticotropin‐releasing Hormone Receptor Type 2 Play an Important Role in Long‐term Ultraviolet A Eye Irradiation‐induced Photoaging

Photoaging is induced by long‐term ultraviolet A (UVA) eye irradiation. However, the mechanism of skin damage due to UVA eye irradiation is still not well understood. In this study, we used C57BL/6j and gp91phox knockout (gp91phox^?/?) mice for the long‐term effects of UVA irradiation. The eye or dorsal skin of the mice was locally exposed to UVA for 12 months. The reactive oxygen species (ROS), gp91phox, corticotropin‐releasing hormone (CRH), urocortin 2, and CRH receptor (CRHR) type 1 and type 2 levels in the brain and mast cell tryptase and histamine levels in the dorsal skin all increased after UVA irradiation. The levels of CRH, urocortin 2, CRHR type 1 and type 2 in the brain also increased more after UVA eye irradiation than after UVA skin irradiation. Moreover, photoaging of the UVA eye irradiation mice was not induced following the administration of a ROS inhibitor in the brain. In addition, in gp91phox^?/? mice, photoaging by UVA eye irradiation was not induced. These results indicate that long‐term UVA eye irradiation led to increased gp91phox‐derived ROS in the brain and the increased expression of urocortin 2 and CRHR type 2, resulting in photoaging; however, further studies are needed to confirm these findings.     

The Injury and Cumulative Effects on Human Skin by UV Exposure from Artificial Fluorescence Emission

The injury and cumulative effects of UV emission from fluorescence lamp were studied. UV intensity from fluorescence lamp was measured, and human skin samples (hips, 10 volunteers) were exposed to low‐dose UV irradiation (three times per week for 13 consecutive weeks). Three groups were examined: control group without UV radiation; low‐dose group with a cumulative dose of 50 J cm^?2 which was equivalent to irradiation of the face during indoor work for 1.5 years; and high‐dose group with 1000 J cm^?2 cumulative dose equivalent to irradiation of the face during outdoor activities for 1 year. Specific indicators were measured before and after UVA irradiation. The findings showed that extending the low‐dose UVA exposure decreased the skin moisture content and increased the transepidermal water loss as well as induced skin color changes (decreased L* value, increased M index). Furthermore, irradiated skin showed an increased thickness of cuticle and epidermis, skin edema, light color and unclear staining collagen fibers in the dermis, and elastic fiber fragmentation. In addition, MMP‐1, p53 and SIRT1 expression was also increased. Long‐term exposure of low‐dose UVA radiation enhanced skin photoaging. The safety of the fluorescent lamp needs our attention.     

Red Light Interferes in UVA‐Induced Photoaging of Human Skin Fibroblast Cells

The possible regulation mechanism of red light was determined to discover how to retard UVA‐induced skin photoaging. Human skin fibroblasts were cultured and irradiated with different doses of UVA, thus creating a photoaging model. Fibroblasts were also exposed to a subtoxic dose of UVA combined with a red light‐emitting diode (LED) for five continuous days. Three groups were examined: control, UVA and UVA plus red light. Cumulative exposure doses of UVA were 25 J cm^?2, and the total doses of red light were 0.18 J cm^?2. Various indicators were measured before and after irradiation, including cell morphology, viability, β‐galactosidase staining, apoptosis, cycle phase, the length of telomeres and the protein levels of photoaging‐related genes. Red light irradiation retarded the cumulative low‐dose UVA irradiation‐induced skin photoaging, decreased the expression of senescence‐associated β‐galactosidase, upregulated SIRT1 expression, decreased matrix metalloproteinase MMP‐1 and the acetylation of p53 expression, reduced the horizon of cell apoptosis and enhanced cell viability. Furthermore, the telomeres in UVA‐treated cells were shortened compared to those of cells in the red light groups. These results suggest that red light plays a key role in the antiphotoaging of human skin fibroblasts by acting on different signaling transduction pathways.     

The Endogenous Tryptophan‐derived Photoproduct 6‐formylindolo[3,2‐b]carbazole (FICZ) is a Nanomolar Photosensitizer that Can be Harnessed for the Photodynamic Elimination of Skin Cancer Cells in Vitro and in Vivo

UV‐chromophores contained in human skin may act as endogenous sensitizers of photooxidative stress and can be employed therapeutically for the photodynamic elimination of malignant cells. Here, we report that 6‐formylindolo[3,2‐b]carbazole (FICZ), a tryptophan‐derived photoproduct and endogenous aryl hydrocarbon receptor agonist, displays activity as a nanomolar sensitizer of photooxidative stress, causing the photodynamic elimination of human melanoma and nonmelanoma skin cancer cells in vitro and in vivo. FICZ is an efficient UVA/Visible photosensitizer having absorbance maximum at 390 nm (ε = 9180 L mol^?1 cm^?1), and fluorescence and singlet oxygen quantum yields of 0.15 and 0.5, respectively, in methanol. In a panel of cultured human squamous cell carcinoma and melanoma skin cancer cells (SCC‐25, HaCaT‐ras II‐4, A375, G361, LOX), photodynamic induction of cell death was elicited by the combined action of solar simulated UVA (6.6 J cm^?2) and FICZ (≥10 nm ), preceded by the induction of oxidative stress as substantiated by MitoSOX Red fluorescence microscopy, comet detection of Fpg‐sensitive oxidative genomic lesions and upregulated stress response gene expression (HMOX1, HSPA1A, HSPA6). In SKH1 “high‐risk” mouse skin, an experimental FICZ/UVA photodynamic treatment regimen blocked the progression of UV‐induced tumorigenesis suggesting feasibility of harnessing FICZ for the photooxidative elimination of malignant cells in vivo.     

Ultraviolet A Eye Irradiation Ameliorates Atopic Dermatitis via p53 and Clock Gene Proteins in NC/Nga Mice

Atopic dermatitis (AD ) is a widespread chronic skin condition that severely affects quality of life and can lead to more serious complications. Although ultraviolet (UV )A eye irradiation can exert various effects on the skin, it is unknown whether UVA can affect AD . To investigate potential associations, we used an NC /Nga mouse model of AD to study the effects of UVA eye irradiation. The eyes of mice were irradiated with a UVA dose of 100 kJ m⁻² using a FL 20SBLB ‐A lamp. Our histological data demonstrated that AD symptoms could be ameliorated by UVA eye irradiation. We also observed an increase in the levels of adrenocorticotropic hormone (ACTH ), p53 and retinoid X receptor α (RXR α ) in mice with UVA ‐irradiated eyes. In contrast, the levels of thymic stromal lymphopoietin (TSLP ), period 2 (PER 2) and differentiated embryo chondrocytes 1 (DEC 1) protein were decreased in mice treated with UVA irradiation. Furthermore, UVA eye‐irradiated mice exhibited reduced DEC 1 and RXR α colocalization compared with nonirradiated mice. These results suggested that p53 and various clock gene proteins played important roles in the amelioration of AD symptoms observed after UVA eye irradiation; this technique may have therapeutic applications in AD .     

The Effects of Ultraviolet Eye Irradiation on Dextran Sodium Sulfate‐Induced Ulcerative Colitis in Mice

Ultraviolet (UV) eye irradiation denatures the cells of the intestine. This study examined the action of UVA and UVB on dextran sodium sulfate (DSS)‐induced ulcerative colitis. We produced a mouse model of ulcerative colitis by administering DSS for 5 days and irradiated the eye with UVB or UVA for each day of the DSS treatment period. DSS‐induced ulcerative colitis was deteriorated by the UVB eye irradiation. Conversely, the symptoms improved with UVA eye irradiation. The levels of adrenocorticotropic hormone (ACTH), corticotropin‐releasing hormone (CRH), urocortin 2, interleukin (IL)‐18, IL‐6 and histamine in the blood increased after the UVB eye irradiation of DSS‐treated mice (UVB/DSS‐treated mice). In contrast, the β‐endorphin level in the blood of the UVA/DSS‐treated mice increased and the levels of urocortin 2, tumor necrosis factor (TNF)‐α and histamine decreased. Furthermore, in the colon, the expression of melanocortin‐2 receptors (MC2R) increased in the UVB/DSS‐treated mice, while the expression of μ‐opioid receptors increased in the UVA/DSS‐treated mice. When an ACTH inhibitor was administered, UVB eye irradiation caused the deterioration of DSS‐treated ulcerative colitis, while the effect of UV eye irradiation disappeared with a μ‐opioid receptor antagonist. These results suggested that UV eye irradiation plays an important role in DSS‐induced ulcerative colitis.     

Differential Activation of Signaling Pathways by UVA and UVB Radiation in Normal Human Epidermal Keratinocytes(†)

Ultraviolet (UV) radiation from the solar spectrum is a major etiological factor for many cutaneous pathologies including cancer. By understanding changes in cell signaling pathways induced by UVA and UVB, novel strategies for prevention and treatment of UV‐related pathologies could be developed. However, much of the information in the literature from various laboratories cannot cross talk because of difficulties associated with the use of ill‐defined light sources and physiologically irrelevant light dosimetry. Herein, we have assessed the effect of exposure of normal human epidermal keratinocytes (NHEK) to UVA (2 and 4 J cm^?2) or UVB (20 and 40 mJ cm^?2) radiation. Employing western blot analysis, we found that exposure of NHEK to UVB, but not UVA, phosphorylates JNK1/2 at Th¹⁸³/Tyr¹⁸⁵, STAT3 at Ser⁷²⁷, AKT at Ser⁴⁷³ and increases c‐Fos expression, whereas exposure to UVA, but not UVB, phosphorylates AKT at Thr³⁰⁸. UVB as well as UVA exposure leads to increased phosphorylation of (1) ERK1/2 at Th²⁰²/Tyr²⁰⁴; (2) p38 at Th¹⁸⁰/Tyr²⁰⁴; (3) STAT3 at Tyr⁷⁰⁵; (4) mTOR at Thr²⁴⁴⁸; and (v) p70S6k at Thr⁴²¹/Ser⁴²⁴; enhanced expression of PI3K (p85) and c‐jun; and nuclear translocation of NFκB proteins. These findings could be considered as a beginning for understanding the differential effects of UVA and UVB in the human skin and may have implications both with respect to risk assessment from exposure to solar UV radiation, and to target interventions against signaling events mediated by UVA and UVB.     

Impact of Long‐Wavelength Ultraviolet A1 and Visible Light on Light‐Skinned Individuals

Solar radiation is known to be a major contributor to the development of skin cancer. Most sunscreen formulations, including those with broad spectrum, offer minimal protection in long‐wavelength ultraviolet A1 (UVA1; 370–400 nm) and visible light (VL; 400–700 nm) domain. There is limited information regarding the impact of this broad waveband (VL + UVA1, 370–700 nm) on those with light skin. In this study, ten healthy adult subjects with Fitzpatrick skin phototypes I–III were enrolled. On day 0, subjects' lower back was exposed to a VL + UVA1 dose of 480 J cm^?2. A statistically significant increase in erythema immediately after irradiation compared with subjects' baseline nonirradiated skin was observed. Clinically perceptible erythema with VL + UVA1 is a novel finding since the erythemogenic spectrum of sunlight has primarily been attributed to ultraviolet B and short‐wavelength ultraviolet A (320–340 nm). The results emphasize the need for protection against this part of the solar spectra and warrant further investigation.     

UVA and UVB‐Induced 8‐Methoxypsoralen Photoadducts and a Novel Method for their Detection by Surface‐Enhanced Laser Desorption Ionization Time‐of‐Flight Mass Spectrometry (SELDI‐TOF MS)

UVA‐activated psoralens are used to treat hyperproliferative skin conditions due to their ability to form DNA photoadducts, which impair cellular processes and may lead to cell death. Although UVA (320–400 nm) is more commonly used clinically, studies have shown that UVB (280–320 nm) activation of psoralen can also be effective. However, there has been no characterization of UVB‐induced adduct formation in DNA alone. As psoralen derivatives have a greater extinction coefficient in the UVB region (11 800 cm^?1 M^?1 at 300 nm) compared with the UVA region (2016 cm^?1 M^?1 at 365 nm), a greater extent of adduct formation is expected. SELDI‐TOF, a proteomic technique that combines chromatography with mass spectrometry, was used to detect photoadduct formation in an alternating A–T oligonucleotide. 8‐Methoxypsoralen (8‐MOP) and DNA solutions were irradiated with either UVA or UVB. An adduct peak was obtained with SELDI‐TOF. For UVB‐activated 8‐MOP, the extent of adducts was three times greater than for UVA. HPLC ESI‐MS analysis showed that UVB irradiation yielded high levels of 3,4‐monoadducts (78% of total adducts). UVA was more effective than UVB at conversion of 4′,5′‐monoadducts to crosslinks (17% vs 4%, respectively). This report presents a method for comparing DNA binding efficiencies of interstrand crosslink inducing agents.     

Interleukin‐17 Mediated Inflammatory Responses Are Required for Ultraviolet Radiation‐Induced Immune Suppression

Ultraviolet radiation (UVR) induces immunosuppression and is a major factor for development of skin cancer. Numerous efforts have been made to determine mechanisms for UVR‐induced immunosuppression and to develop strategies for prevention and treatment of UVR‐induced cancers. In the current study, we use IL‐17 receptor (IL‐17R) deficient mice to examine whether IL‐17 mediated responses have a role in UVB (290–320)‐induced immunosuppression of contact hypersensitivity responses. Results demonstrate that IL‐17 mediated responses are required for UVB‐induced immunosuppression of contact hypersensitivity responses. The systemic immune suppression and development of regulatory T cells are inhibited in UVB‐treated IL‐17R deficient mice compared to wild‐type animals. The deficiency in IL‐17R inhibits the infiltration and development of a tolerogenic myeloid cell population in UVB‐treated skin, which expresses CD11b and Gr‐1 and produces reactive oxygen species. We speculate that the development of the tolerogenic myeloid cells is dependent on IL‐17‐induced chemokines and inflammatory mediators in UVB‐treated skin. The inhibition of the tolerogenic myeloid cells may be attributed to the suppression of regulatory T cells in UVR‐treated IL‐17R^?/? mice. The findings may be exploited to new strategies for prevention and treatment of UVR‐induced skin diseases and cancers.     

Requirement for Metalloproteinase‐dependent ERK and AKT Activation in UVB‐induced G1‐S Cell Cycle Progression of Human Keratinocytes

UVB (280–315 nm) in natural sunlight represents a major environmental challenge to the skin and is clearly associated with human skin cancer. Here we demonstrate that low doses of UVB induce keratinocyte proliferation and cell cycle progression of human HaCaT keratinocytes. Different from UVA, UVB irradiation induced extracellular signal‐regulated kinase (ERK) and AKT activation and their activation are both required for UVB‐induced cell cycle progression. Activation of epidermal growth factor receptor (EGFR) was observed after UVB exposure and is upstream of ERK/AKT/cyclin D1 pathway activation and cell cycle progression following UVB radiation. Furthermore, metalloproteinase (MP) inhibitor GM6001 blocked UVB‐induced ERK and AKT activation, cell cycle progression, and decreased the EGFR phosphorylation, demonstrating that MPs mediate the EGFR/ERK/AKT/cyclin D1 pathways and cell cycle progression induced by UVB radiation. In addition, ERK or AKT activation is essential for EGFR activation because ERK or AKT inhibitor blocks EGFR activation following UVB radiation, indicating that EGFR/AKT/ERK pathways form a regulatory loop and converge into cell cycle progression following UVB radiation. Identification of these signaling pathways in UVB‐induced cell cycle progression of quiescent keratinocytes as a process mimicking tumor promotion in vivo will facilitate the development of efficient and safe chemopreventive and therapeutic strategies for skin cancer.     

Protective Effect of Baicalin Against TLR4‐mediated UVA‐induced Skin Inflammation

UVA irradiation is known to cause photoaging via production of reactive oxygen species (ROS) and activation of inflammatory processes. Previously, we have demonstrated that baicalin, a plant‐derived flavonoid possessing both antioxidant and anti‐inflammatory activity, protects mouse keratinocytes against damage from UVB irradiation. However, the role of baicalin in vivo has not been well studied, particularly in the setting of UVA irradiation. To explore the protective effects and mechanisms of baicalin treatment in mice after UVA irradiation, mice were exposed to acute and chronic doses of UVA irradiation with or without baicalin or vehicle. Skin samples were collected for histological staining, RNA isolation, flow cytometry and protein extraction. Our results demonstrate the protective effect of baicalin against UVA‐induced oxidative damage and inflammation in mouse skin. These effects are likely mediated via the TLR4 pathway, which may serve as a target for photochemoprevention against skin inflammation.     

Dietary Feeding of Opuntia Humifusa Inhibits UVB Radiation‐Induced Carcinogenesis by Reducing Inflammation and Proliferation in Hairless Mouse Model

It has been validated that ultraviolet B (UVB) irradiation induced both squamous and basal cell carcinomas, as a tumor initiator and promoter. Opuntia humifusa is a member of the Cactaceae family which has been demonstrated in our previous study to have a chemopreventive effect in 7, 12‐dimethylbenz[a]anthracene and 12‐O‐tetradecanoylphorbol‐13‐acetate induced skin carcinogenesis models. Therefore, this study was designed to determine the protective effects of O.humifusa against photocarcinogenesis. O. humifusa was administrated to mice as a dietary feeding, following exposure to UVB radiation (180 mJ/cm²) twice a week of 30 weeks for skin tumor development in hairless mice. Dietary O.humifusa inhibited UVB‐induced epidermal hyperplasia, infiltration of leukocytes, level of myeloperoxidase and the levels of proinflammatory cytokines, tumor necrosis factor‐ α (TNF‐α), interleukin‐1β (IL‐1β) and interleukin‐6 (IL‐6), in UVB exposed skin. Also, O.humifusa significantly inhibited both protein and mRNA expression level of cyclooxygenase‐2 (COX‐2), nitric oxide synthase (iNOS), proliferating cell nuclear antigen (PCNA) and cyclin D1 compared to the non‐O.humifusa treated group. Collectively, these results suggest that O.humifusa could inhibit photocarcinogenesis in mouse skin and that protective effect is associated with the inhibition of not only UVB‐induced inflammatory responses involving COX‐2, iNOS and proinflammatory cytokines, but also the down‐regulation of UVB‐induced cellular proliferation.     

Distinct Role of Sesn2 in Response to UVB‐Induced DNA Damage and UVA‐Induced Oxidative Stress in Melanocytes

Ultraviolet (UV) radiation, including both UVB and UVA irradiation, is the major risk factor for causing skin cancer including melanoma. Recently, we have shown that Sesn2, a member of the evolutionarily conserved stress‐inducible protein family Sestrins (Sesn), is upregulated in human melanomas as compared to melanocytes in normal human skin, suggesting an oncogenic role of Sesn2. However, the role of Sesn2 in UVB and UVA response is unknown. Here, we demonstrated that both UVB and UVA induce Sesn2 upregulation in melanocytes and melanoma cells. UVB induces Sesn2 expression through the p53 and AKT3 pathways. Sesn2 negatively regulates UVB‐induced DNA damage repair. In comparison, UVA induces Sesn2 upregulation through mitochondria but not Nrf2. Sesn2 ablation increased UVA‐induced Nrf2 induction and inhibits UVA‐induced ROS production, indicating that Sesn2 acts as an upstream regulator of Nrf2. These findings suggest previously unrecognized mechanisms in melanocyte response to UVB and UVA irradiation and potentially in melanoma formation.     

Expression and Function of Macrophage Migration Inhibitory Factor in the Pathogenesis of UV-Induced Cutaneous Nonmelanoma Skin Cancer(†)

Chronic skin exposure to ultraviolet light stimulates the production of cytokines known to be involved in the initiation of skin cancer. Recent studies in mouse models suggested a role for macrophage migration inhibitory factor (MIF) in the UVB‐induced pathogenesis of nonmelanoma skin cancer (NMSC). Our studies aimed at defining the pathophysiological function of MIF in cutaneous inflammatory reactions and in the development and progression of NMSC. Immunohistochemical analysis revealed a moderate expression of MIF in normal human skin samples but an enhanced expression of this cytokine in lesional skin of patients with actinic keratosis or cutaneous SCC. Enzyme‐linked immunosorbent assay studies showed a time‐dependent increase in MIF secretion after a moderate single‐dose UVB irradiation in NHEKs and SCC tumor cells. MIF is known to interact with CXCR2, CXCR4 and CD74. These receptors are not constitutively expressed in keratinocytes and HaCaT cells and their expression is not induced by UVB irradiation either. However, stimulation with IFNγ upregulated CD74 surface expression in these cells. Affymetrix^® Gene Chip analysis revealed that only keratinocytes prestimulated with IFNγ are responsive to MIF. These findings indicate that MIF may be an important factor in the pathogenesis of NMSC tumorigenesis and progression in an inflammatory environment.     

Synthesis and characterization of anhydrous conducting polyimide/ionic liquid complex membranes via a new route for high‐temperature fuel cells

The paper deals with the synthesis and characterization of a new series of anhydrous conducting acid‐doped complex membranes based on polyimide (PI) and ionic liquid (IL) for high‐temperature fuel cells via a new route. For this purpose, three imidazolium‐based ILs (RIm⁺BF₄^?) with different alkyl chain lengths (R=methyl, ethyl, and butyl) are added into polyamic acid (PAA) intermediate prepared from the reaction of benzophenonetetracarboxylic dianhydride and diaminodiphenylsulfone in different –COOH/imidazolium molar ratios (n = 0.5, 1, and 2). Then, the thermally imidized complex membrane was doped with H₂SO₄. The conductivities of acid‐doped PI/IL complex membranes prepared by taking n of 1 are found to be in the range of 10^?4?10^?5 S cm^?1 at 180°C, whereas the acid‐free PI/IL complex membranes show the conductivity at around 10^?9?10^?10 S cm^?1. Thermogravimetric analysis results reveal that the acid‐doped PI/IL complex membranes are thermally stable up to 250°C. Dynamic mechanical analysis results of the acid‐doped ionically interacted complex membrane show that the mechanical strengths of the PI/IL complex membranes including 1‐methyl imidazolium tetrafluoroborate (MeIm‐BF₄) and 1‐ethyl 3‐methyl imidazolium tetrafluoroborate (EtIm‐BF₄) are comparable with those of pristine PI until 200°C. Furthermore, it can be clearly emphasized that the ionic interaction between carboxylic acid groups of PAA's and IL's cations offers a positive role in long‐term conductivity stability by preventing the IL migration at high temperatures. On the other hand, preliminary methanol permeability tests of the acid‐doped membranes show that they can also be considered as an alternative for direct methanol fuel cells. Copyright © 2011 John Wiley & Sons, Ltd.     

Proanthocyanidins from Grape Seeds Inhibit UV–Radiation‐Induced Immune Suppression in Mice: Detection and Analysis of Molecular and Cellular Targets

Ultraviolet (UV)–radiation‐induced immunosuppression has been linked with the risk of skin carcinogenesis. Approximately, 2 million new cases of skin cancers, including melanoma and nonmelanoma, diagnosed each year in the USA and therefore have a tremendous bad impact on public health. Dietary phytochemicals are promising options for the development of effective strategy for the prevention of photodamaging effects of UV radiation including the risk of skin cancer. Grape seed proanthocyanidins (GSPs) are such phytochemicals. Dietary administration of GSPs with AIN76A control diet significantly inhibits UV‐induced skin tumor development as well as suppression of immune system. UV‐induced suppression of immune system is commonly determined using contact hypersensitivity (CHS) model which is a prototype of T–cell‐mediated immune response. We present evidence that inhibition of UV‐induced suppression of immune system by GSPs is mediated through: (i) the alterations in immunoregulatory cytokines, interleukin (IL)‐10 and IL‐12, (ii) DNA repair, (iii) stimulation of effector T cells and (iv) DNA repair‐dependent functional activation of dendritic cells in mouse model. These information have important implications for the use of GSPs as a dietary supplement in chemoprevention of UV‐induced immunosuppression as well as photocarcinogenesis.     

Effects and Mechanism of Nicotinamide Against UVA‐ and/or UVB‐mediated DNA Damages in Normal Melanocytes

Melanoma incidences are increasing rapidly, and ultraviolet (UV) radiation from the sun is believed to be its major contributing factor. UV exposure causes DNA damage in skin which may initiate cutaneous skin cancers including melanoma. Melanoma arises from melanocytes, the melanin‐producing skin cells, following genetic dysregulations resulting into hyperproliferative phenotype and neoplastic transformation. Both UVA and UVB exposures to the skin are believed to trigger melanocytic hyperplasia and melanomagenesis. Melanocytes by themselves are deficient in repair of oxidative DNA damage and UV‐induced photoproducts. Nicotinamide, an active form of vitamin B3 and a critical component of the human body's defense system has been shown to prevent certain cancers including nonmelanoma skin cancers. However, the mechanism of nicotinamide's protective effects is not well understood. Here, we investigated potential protective effects and mechanism of nicotinamide against UVA‐ and/or UVB‐ induced damage in normal human epidermal melanocytes. Our data demonstrated an appreciable protective effect of nicotinamide against UVA‐ and/or UVB‐ induced DNA damage in melanocytes by decreasing both cyclobutane pyrimidine dimers and 8‐hydroxy‐2′‐deoxyguanosine levels. We found that the photoprotective response of nicotinamide was associated with the activation of nucleotide excision repair genes and NRF2 signaling. Further studies are needed to validate our findings in in vivo models.