ArticlePDF Available

Abstract and Figures

Skin damage from exposure to sunlight induces aging-like changes in appearance and is attributed to the ultraviolet (UV) component of light. Photosensitized production of reactive oxygen species (ROS) by UVA light is widely accepted to contribute to skin damage and carcinogenesis, but visible light is thought not to do so. Using mice expressing redox-sensitive GFP to detect ROS, blue light could produce oxidative stress in live skin. Blue light induced oxidative stress preferentially in mitochondria, but green, red, far red or infrared light did not. Blue light-induced oxidative stress was also detected in cultured human keratinocytes, but the per photon efficacy was only 25% of UVA in human keratinocyte mitochondria, compared to 68% of UVA in mouse skin. Skin autofluorescence was reduced by blue light, suggesting flavins are the photosensitizer. Exposing human skin to the blue light contained in sunlight depressed flavin autofluorescence, demonstrating that the visible component of sunlight has a physiologically significant effect on human skin. The ROS produced by blue light is probably superoxide, but not singlet oxygen. These results suggest that blue light contributes to skin aging similar to UVA.
Content may be subject to copyright.
A preview of the PDF is not available
... Among all ROS, O 2 −· and • OH are free radicals, and • OH is known to be the most reactive [22]. • OH is produced by the Fenton reaction [23] between transition metal ions such as Cu 2+ and Fe 2+ and H 2 O 2 , and by irradiation of H 2 O 2 with light in the ultraviolet (UV) to blue light range [24]. Therefore, the • OH produced by photolysis of H 2 O 2 is applied in dentistry for sterilization [25][26][27][28][29][30][31] and tooth bleaching [32,33]. ...
... Among all ROS, O2 − ・ and • OH are free radicals, and • OH is known to be the mos reactive [22]. • OH is produced by the Fenton reaction [23] between transition metal ion such as Cu 2+ and Fe 2+ and H2O2, and by irradiation of H2O2 with light in the ultraviole (UV) to blue light range [24]. Therefore, the • OH produced by photolysis of H2O2 is ap plied in dentistry for sterilization [25][26][27][28][29][30][31] and tooth bleaching [32,33]. ...
... The wavelength spectrum used for the photolysis reaction of H2O2 ranges from UV to blue light, In these systems, • OH generated by the photolysis of H 2 O 2 in reactive systems has been applied to oral bacterial infections, such as caries [25,70,71], periodontal disease [25,27,72], periapical disease [25,71], and aspiration pneumonia [25,26,29,59]. The wavelength spectrum used for the photolysis reaction of H 2 O 2 ranges from UV to blue light, which is visible light [24]. Therefore, many reports in the dental field use a wavelength of 405 nm to generate • OH [25][26][27][28][29][30][31]58,59,70,71]. ...
Article
Full-text available
Reactive oxygen species (ROS) and free radicals, which have been implicated in inflammation, pain, carcinogenesis, and aging, are actually used in dental treatments such as tooth bleaching and composite resin polymerization. Recently, numerous studies have investigated the application of ROS in the medical and dental fields. In previous studies, ROS were generated intentionally through pathways such as photolysis, photocatalytic methods, and photodynamic therapy, which are used in the medical field to target cancer. In the field of dentistry, generated ROS are applied mainly for periodontal treatment and sterilization of the root canal, and its effectiveness as an antibacterial photodynamic therapy has been widely reported.. Given this background, the present article aimed to review the basic effects of ROS in dental medicine, especially endodontic therapy, and to discuss future applications of ROS.
... It has been proposed that small increases in ROS production lead to an increase in cell proliferation, whilst a large increase can induce apoptotic signalling pathways. It has been established that blue light could produce oxidative stress in live mouse skin, preferentially in mitochondria, but green, red, far red, or infrared light did not [76]. It was further shown that blue light induced oxidative stress in cultured human keratinocytes. ...
... Exposing human skin to the blue light contained in sunlight depressed Flavin autofluorescence. It has been suggested that blue light could contribute to the same biological effects (skin ageing and an increase in pigmentation) as UVA radiation because wavelengths of blue light are closely related to the UVA spectrum [76,77]. However, it has been stated in some earlier studies that visible blue light does not cause DNA damage or early photo-ageing and that the use thereof in dermatological practice was safe (420 nm at 20 J/cm 2 on five consecutive days) [77]. ...
... Nakashima et al. [76] Human live skin Photodynamic therapy (PDT) lamp with an emission spectrum between 380 and 480 nm and peak emission at 420 nm. Irradiation was given on five consecutive days with 20 J/cm 2 , with a cumulative dose of 100 J/cm 2 . ...
Article
Full-text available
Diabetes is a serious threat to global health and is among the top 10 causes of death. The Diabetic foot ulcer (DFU) is among the most common and severe complications of the disease. Bacterial infections are common; therefore, timely aggressive management, using multidisciplinary management approaches is needed to prevent complications, morbidity, and mortality, particularly in view of the growing cases of antibiotic-resistant bacteria. Photobiomodulation (PBM) involves the application of low-level light at specific wavelengths to induce cellular photochemical and photophysical responses. Red and near-infrared (NIR) wavelengths have been shown to be beneficial, and recent studies indicate that other wavelengths within the visible spectrum could be helpful as well, including blue light (400–500 nm). Reports of the antimicrobial activity and susceptibility of blue light on several strains of the same bacterium show that many bacteria are less likely to develop resistance to blue light treatment, meaning it is a viable alternative to antibiotic therapy. However, not all studies have shown positive results for wound healing and fibroblast proliferation. This paper presents a critical review of the literature concerning the use of PBM, with a focus on blue light, for tissue healing and diabetic ulcer care, identifies the pros and cons of PBM intervention, and recommends the potential role of PBM for diabetic ulcer care.
... heritable aberrations [21]. Blue light exposure has been shown to reduce flavin autofluorescence in the skin of human volunteers [14]. In addition to flavins and porphyrins, Mizutani et al. have shown that both UV and blue light induce ROS generation from carbonylated proteins located in the stratum corneum [13]. ...
Article
The growing use of electronic devices and other artificial light sources in recent decades has changed the pattern of exposure to blue light (400–500 nm). Although some progress has been made in the study of the biological effects of blue light on the skin, many questions in this field remain unexplored. The aim of this article was to review the currently available evidence on the deleterious effects of blue light on the skin, as well as the methods and strategies designed to protect from the detrimental effects of blue light. PubMed and ProQuest databases were searched in January 2022. Search results were supplemented by articles considered relevant by the authors. The results of in vitro, in vivo and clinical studies show that blue light produces direct and indirect effects on the skin. The most significant direct effects are the excessive generation of reactive oxygen and nitrogen species, and hyperpigmentation. Reactive oxygen and nitrogen species cause DNA damage and modulate the immune response. Indirect effects of blue light include disruption of the central circadian rhythm regulation via melatonin signaling and local circadian rhythm regulation via direct effects on skin cells. Antioxidants and sunscreens containing titanium dioxide, iron oxides, and zinc oxide can be used to protect against the detrimental effects of blue light as part of a strategy that combines daytime protection and night-time repair. Blue light produces a wide variety of direct and indirect effects on the skin. As exposure to blue light from artificial sources is likely to continue to increase, this area warrants further investigation.
... For example, extended exposure to blue (but not green or red) light resulted in increased expression of neuronal activityregulated genes in cortical neurons in vitro 29 . Further, studies of human fibroblasts in vitro and in vivo show that BL at different wavelengths and intensity may induce varying degrees of oxidative stress and inhibit proliferation, which could contribute to premature skin photo-aging 16,30 . Of note, it was reported that BL can penetrate human skin to regulate physiology of subcutaneous white adipocytes 31 . ...
Article
Full-text available
Blue light is a predominant component of light emitting devices (LEDs), which are increasingly present in our environment. There is already accumulating evidence that blue light exposure causes damage to retinal cells in vitro and in vivo; however, much less is known about potential effects of blue light on non-retinal cells. That blue light may be detrimental at the organismal level independent from retinal effect was recently shown by findings that it reduces lifespan in worms and also in flies with genetically ablated retinas. Here, we investigated the effects of blue light exposure across the fly lifespan and found that susceptibility to blue light stress is strongly age-dependent. The blue light of the same intensity and duration reduced survival and increased neurodegeneration more significantly in old flies than in young flies. These differences appear to be caused, at least in part, by impairments of mitochondrial respiratory function. We report that blue light significantly reduces the activity of Complex II in the electron transport system and decrease the biochemical activity of succinate dehydrogenase in both young and old flies. In addition, complex I and complex IV activities are reduced by age, as are ATP levels. We therefore propose that older flies are more sensitive to blue light because the light-induced mitochondrial damage potentiates the age-related impairments in energy metabolism that occurs even in darkness. Taken together, our results show that damaging effects of blue light at the organismal level are strongly age dependent and are associated with reduced activity of specific components of energy producing pathways in mitochondria.
... Skin pigmentation has been an important topic related to the health effects of electromagnetic fields (EMF). According to a previous study, skin pigmentation in zebrafish was induced by pulsed electromagnetic fields (PEMFs) (60 Hz) through increasing the activity of TRP-1, which is mediated by the phosphorylation of ERK and p38 [37], reflecting how melanin synthesis and melanocytes may be affected by EMFs [38]. Also, the exposure to extremely low-frequency (ELF) EMFs at low intensities can stimulate melanogenesis in melanocytes [39]. ...
Article
Full-text available
Recently, the impacts of 5G electromagnetic radiation (EMR) with 28 GHz on human health have been attracting public attention with the advent of 5G wireless communication. Here, we report that 5G (28 GHz) EMR can attenuate the skin pigmentation in murine melanoma cells (B16F10) and a 3D pigmented human epidermis model (Melanoderm™). B16 cells were exposed to 5G (28 GHz) with or without α-MSH for 4 h per day. Interestingly, 5G attenuated α-MSH-induced melanin synthesis. Fontana–Masson staining confirmed that the dendritic formation of α-MSH stimulated B16 cells was diminished by 5G exposure. To confirm the anti-melanogenic effect of 5G EMR, MelanoDerm™ was irradiated with 5G at a power intensity of 10 W/m2 for 4 h a day for 16 days and melanin distribution was detected with Fontana–Masson staining, which supported the anti-melanogenic effect of 5G EMR. Consistently, 5G EMR suppressed α-MSH induced upregulation of melanogenic enzymes; tyrosinase, TRP-1, and TRP-2. Of note, 5G EMR attenuated ROS production stimulated by α-MSH and H2O2, suggesting that 5G EMR may dissipate ROS generation, which is pivotal for the melanin synthesis. Collectively, we demonstrated that 5G EMR can attenuate skin pigmentation by attenuating ROS generation.
... Ionizing radiation commonly leads to excessive reactive oxygen species (ROS) generation, which eventually contributes to the interruption of mitochondrial structure and function in many tissues and cells, such as skin, bone marrow mesenchymal stem cells, retinal precursor cells, and salivary gland cells [9][10][11][12]. Mitochondria are associated with numerous essential cellular functions, including ROS generation and scavenging, ATP production, intracellular Ca 2+ signaling, and cell apoptosis [13]. ...
Article
Full-text available
Radiotherapy for patients with head and neck cancer inevitably causes radiation damage to salivary glands (SGs). Overproduction of reactive oxygen species (ROS) leads to mitochondrial damage and is critical in the pathophysiology of SG radiation damage. However, mitochondrial-targeted treatment is unavailable. Herein, both in vitro and in vivo models of radiation-damaged rat submandibular glands (SMGs) were used to investigate the potential role of salidroside in protecting irradiated SGs. Cell morphology was observed with an inverted phase-contrast microscope. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), mitochondrial ROS, mitochondrial membrane potential (MMP), and ATP were measured using relevant kits. The mitochondrial ultrastructure was observed under transmission electron microscopy. Cell apoptosis was determined by Western blot and TUNEL assays. Saliva was measured from Wharton’s duct. We found that salidroside protected SMG cells and tissues against radiation and improved the secretion function. Moreover, salidroside enhanced the antioxidant defense by decreasing MDA, increasing SOD, CAT, and GSH, and scavenging mitochondrial ROS. Furthermore, salidroside rescued the mitochondrial ultrastructure, preserved MMP and ATP, suppressed cytosolic cytochrome c and cleaved caspase 3 expression, and inhibited cell apoptosis. Together, these findings first identify salidroside as a mitochondrial-targeted antioxidant for preventing SG radiation damage.
Article
Background: Ultraviolet (UV) radiation is a well-known factor that causes skin aging. Recently, with the development of technology, the skin has been exposed to not only the UV radiation but also the blue light from electronic devices. Blue light is a high-energy visible light that penetrates deep into the dermal layer, producing reactive oxygen species (ROS) and resulting in skin aging. In this study, we searched for candidate materials that can inhibit blue light-induced skin aging and found Caesalpinia sappan extract (CSE) to be effective. Methods: Human dermal fibroblasts (HDFs) were treated with various concentrations of CSE and brazilin and exposed to blue light. We measured that antioxidant activity, MMP-1 levels using MMP-1 ELISA, changes in collagen type 1, collagen type 3, MMP-1, and MMP-3 mRNA expressions, and ROS generation. Results: We confirmed that CSE has high absorption of blue light and antioxidant activity. Blue light irradiation at 30 J/cm2 decreased the expression of collagen types 1 and 3, increased the expression of matrix metalloproteinase (MMP)-1 and 3, and decreased the production of ROS in human dermal fibroblasts as compared to those of the non-irradiated group. However, pretreatment with CSE protected against the damage caused by the blue light. Brazilin, a major constituent of C. sappan, had high absorbance in the blue region and antioxidant activities. Pretreatment with brazilin also inhibited the damage caused by the blue light in the cells. Conclusion: CSE and brazilin are potential agents for inhibiting skin aging caused by blue light-induced damage.
Article
Visible red light (RL) therapy is a rapidly expanding treatment option for dermatological conditions, including acne, psoriasis, and chronic wounds. It is currently unknown if high fluences of RL induce DNA damage via reactive oxygen species (ROS) stress or other pathways. Our lab previously demonstrated that RL generates ROS in human dermal fibroblasts (HDFs). Other studies show that UV and blue light generate ROS and DNA damage in fibroblasts. This study aims to determine if RL induces DNA damage in HDFs. We found that 320 J/cm2, 640 J/cm2, and 1280 J/cm2 RL (633 ± 6 nm) did not induce measurable DNA damage in the form of cyclobutane pyrimidine dimers (CPD) or 6‐4 photoproducts (6‐4PP) immediately, three hours, and twenty‐four hours following irradiation. Our study further supports that RL therapy is safe and does not induce DNA damage in the form of CPDs or 6‐4PPs in human skin fibroblasts. This article is protected by copyright. All rights reserved.
Chapter
Age-related macular degeneration (AMD) is a complex, degenerative and progressive chronic disease that leads to severe visual loss. The prevalence of early AMD accounts for 18% in the population between 65 and 74 years of age and even 30% in subjects older than 74 years. The articles published in the last decade point out to a significant role of oxidative stress in the onset and development of age-related macular degeneration. Generally, reactive oxygen species (ROS) are produced in the eye during light absorption and physiological metabolic processes. The level of oxidative stress is kept under control by the action of antioxidants and reparative enzymes. Excessive synthesis of ROS leads to increased oxidative modification of lipids, proteins and DNA, causing oxidative damage of cytoplasmic and nuclear cell elements and changes of the extracellular matrix. The accumulation of oxidatively modified compounds in drusen deposits will initiate the onset and development of AMD. The objective of this review was to highlight the mechanisms of oxidative stress in order to elucidate their significance and association with the pathogenesis of AMD.
Article
Full-text available
Genetically encoded probes based on the H2O2-sensing proteins OxyR and Orp1 have greatly increased the ability to detect elevated H2O2 levels in stimulated or stressed cells. However, these proteins are not sensitive enough to monitor metabolic H2O2 baseline levels. Using yeast as a platform for probe development, we developed two peroxiredoxin-based H2O2 probes, roGFP2-Tsa2ΔCR and roGFP2-Tsa2ΔCPΔCR, that afford such sensitivity. These probes are ∼50% oxidized under 'normal' unstressed conditions and are equally responsive to increases and decreases in H2O2. Hence, they permit fully dynamic, real-time measurement of basal H2O2 levels, with subcellular resolution, in living cells. We demonstrate that expression of these probes does not alter endogenous H2O2 homeostasis. The roGFP2-Tsa2ΔCR probe revealed real-time interplay between basal H2O2 levels and partial oxygen pressure. Furthermore, it exposed asymmetry in H2O2 trafficking between the cytosol and mitochondrial matrix and a strong correlation between matrix H2O2 levels and cellular growth rate.
Article
Full-text available
Background: Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss. Objective: To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity. Design: The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. Main outcome measures: (1) Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline (> or =15 letters). Primary analyses used repeated-measures logistic regression with a significance level of.01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. Results: Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations. Conclusions: Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study.
Article
Full-text available
Fluorescent protein sensors have re-vitalized the field of redox biology by revolutionizing the study of redox processes in living cells and organisms. Recent Advances: Within one decade a set of fundamental new insights has been gained, driven by the rapid technical development of in vivo redox sensing. Redox-sensitive yellow and green fluorescent protein variants (rxYFP and roGFPs) have been the central players. Although widely used as an established standard tool, important questions remain surrounding their meaningful use in vivo. We review the growing range of thiol redox sensor variants and their application in different cells, tissues and organisms. We highlight five key findings where in vivo sensing has been instrumental in changing our understanding of redox biology, critically assess the interpretation of in vivo redox data and discuss technical and biological limitations of current redox sensors and sensing approaches. We explore how novel sensor variants may further add to the current momentum towards a novel mechanistic and integrated understanding of redox biology in vivo.
Article
Full-text available
Mutations in sunlight-induced melanoma arise from cyclobutane pyrimidine dimers (CPDs), DNA photoproducts that are typically created picoseconds after an ultraviolet (UV) photon is absorbed at thymine or cytosine. We found that in melanocytes, CPDs are generated for >3 hours after exposure to UVA, a major component of the radiation in sunlight and in tanning beds. These "dark CPDs" constitute the majority of CPDs and include the cytosine-containing CPDs that initiate UV-signature C→T mutations. Dark CPDs arise when UV-induced reactive oxygen and nitrogen species combine to excite an electron in fragments of the pigment melanin. This creates a quantum triplet state that has the energy of a UV photon but induces CPDs by energy transfer to DNA in a radiation-independent manner. Melanin may thus be carcinogenic as well as protective against cancer. These findings also validate the long-standing suggestion that chemically generated excited electronic states are relevant to mammalian biology. Copyright © 2015, American Association for the Advancement of Science.
Article
Most of us know there is a payoff to looking good, and in the quest for beauty we spend countless hours and billions of dollars on personal grooming, cosmetics, and plastic surgery. But how much better off are the better looking? Based on the evidence, quite a lot. The first book to seriously measure the advantages of beauty,Beauty Paysdemonstrates how society favors the beautiful and how better-looking people experience startling but undeniable benefits in all aspects of life. Noted economist Daniel Hamermesh shows that the attractive are more likely to be employed, work more productively and profitably, receive more substantial pay, obtain loan approvals, negotiate loans with better terms, and have more handsome and highly educated spouses. Hamermesh explains why this happens and what it means for the beautiful--and the not-so-beautiful--among us. Exploring whether a universal beauty standard exists, Hamermesh illustrates how attractive workers make more money, how these amounts differ by gender, and how looks are valued differently based on profession. The author wonders whether extra pay for good-looking people represents discrimination, and, if so, who is discriminating. He investigates the commodification of beauty in dating and how this influences the search for intelligent or high-earning mates, and even considers whether government programs should aid the ugly. Hamermesh also discusses whether the economic benefits of beauty will persist into the foreseeable future and what the "looks-challenged" can do to overcome their disadvantage. © Daniel S. Hamermesh Princeton University Press. All Rights Reserved.
Article
The photochemical aspects of flavins have been reviewed with reference to the analysis of flavins and photoproducts in degraded solutions, spectral and photophysical properties, photodegradation reactions, photosensitization reactions, and photostability of riboflavin in pharmaceutical preparations. The photochemistry of flavins in aqueous solution involves two major photodegradation reactions, viz intramolecular photoreduction and photoaddition, occurring separately or concomitantly in the presence of phosphate buffer, leading to the formation of lumichrome and cyclodehydroriboflavin, respectively. The photoreduction is catalyzed by H2PO4- ions and the photoaddition by HPO42− ions. Intermolecular photoreduction also takes place in a large number of flavin-substrate interactions involving the flavin triplet state. Knowledge of the spectral and photophysical properties, and photochemical behaviour of flavins is necessary to understand the nature of flavin–protein interactions, flavin photosensitization reactions, and their role in biological processes. The study of the photochemical behaviour of riboflavin as a function of pH is a prerequisite to achieve optimum stability of the vitamin in pharmaceutical preparations. Technological processes are being developed to utilize riboflavin as a photosensitizer in the pathogenic inactivation of blood components. Riboflavin-sensitized photooxidation of amino acids in protein may have important biological implications to control photoinduced damage in biological systems. The application of femtosecond-resolved fluorescence spectroscopy and transient absorption techniques may provide useful information on the dynamics of flavoproteins.
Article
Integrity of human skin is endangered by exposure to UV irradiation and chemical stressors, which can provoke a toxic production of reactive oxygen species (ROS) and oxidative damage. Since oxidation of proteins and metabolites occurs virtually instantaneously, immediate cellular countermeasures are pivotal to mitigate the negative implications of acute oxidative stress. We investigated the short-term metabolic response in human skin fibroblasts and keratinocytes to H2O2 and UV exposure. In time-resolved metabolomics experiments, we observed that within seconds after stress induction, glucose catabolism is routed to the oxidative pentose phosphate pathway (PPP) and nucleotide synthesis independent of previously postulated blocks in glycolysis (i.e., of GAPDH or PKM2). Through ultra-short (13)C labeling experiments, we provide evidence for multiple cycling of carbon backbones in the oxidative PPP, potentially maximizing NADPH reduction. The identified metabolic rerouting in oxidative and non-oxidative PPP has important physiological roles in stabilization of the redox balance and ROS clearance. Copyright © 2015 Elsevier Inc. All rights reserved.
Article
‐ ) and a Fenton reaction — could be involved. endonuclease V (i.e. cyclobutane pyrimidine dimers) was Yet another possibility is a release of Ca 21 from intracellular constant (~1:200), indicating that the direct excitation of stores which could activate cellular nucleases and thus induce DNA is responsible for both types of damage in this range DNA damage (18,19). of the spectrum. While the yield of pyrimidine dimers per The ratio of pyrimidine dimers and oxidative DNA modiunit dose continued to decrease exponentially beyond 315 fications at various wavelengths depends on the relative connm, the yield of Fpg-sensitive modifications increased to a tribution of direct and indirect mechanisms and is of major second maximum between 400 and 450 nm. The damage interest for the estimation of the mutagenic risk associated spectrum in this wavelength range consisted of only a with solar irradiation and the impact of spectral changes caused few other modifications (strand breaks, abasic sites and by ozone layer depletion. Here, we report a quantification of pyrimidine modifications sensitive to endonuclease III) cyclobutane pyrimidine dimers and various types of oxidative and is attributed to endogenous photosensitizers that give modifications induced in cultured cells by wavelengths between rise to oxidative DNA damage via singlet oxygen and/or 290 and 500 nm. The lesions were quantified by means of type I reactions. The generation of Fpg-sensitive modifica- several repair endonucleases (Table I) and an alkaline elution tions by visible light was not linear with dose but followed technique (28). a saturation curve. It is calculated that the exposure of the The results indicate that the generation of oxidative DNA cells to low doses of solar radiation results in the formation base modifications by solar radiation has a second maximum of cyclobutane pyrimidine dimers and Fpg-sensitive modi- between 400 and 450 nm due to the excitation of (unidentified) fications in a ratio of 10:1. endogenous photosensitizers and that in cells exposed to sunlight these indirectly induced base modifications account for ~10% of the total endonuclease-sensitive base damage.
Article
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is best known for mediating the toxicity and tumour-promoting properties of the carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as 'dioxin'. AHR influences the major stages of tumorigenesis - initiation, promotion, progression and metastasis - and physiologically relevant AHR ligands are often formed during disease states or during heightened innate and adaptive immune responses. Interestingly, ligand specificity and affinity vary between rodents and humans. Studies of aggressive tumours and tumour cell lines show increased levels of AHR and constitutive localization of this receptor in the nucleus. This suggests that the AHR is chronically activated in tumours, thus facilitating tumour progression. This Review discusses the role of AHR in tumorigenesis and the potential for therapeutic modulation of its activity in tumours.