Geographic distribution of environmental factors influencing human skin coloration

Skin coloration in indigenous peoples is strongly related to levels of ultraviolet radiation (UVR). In this study, the relationships of skin reflectance to seasonal UVR levels and other environmental variables were investigated, with the aim of determining which variables contributed most significantly to skin reflectance. The UVR data recorded by satellite were combined with environmental variables and data on human skin reflectance in a geographic information system (GIS). These were then analyzed visually and statistically through exploratory data analysis, correlation analysis, principal components analysis, least-squares regression analysis, and nonlinear techniques. The main finding of this study was that the evolution of skin reflectance could be almost fully modeled as a linear effect of UVR in the autumn alone. This linear model needs only minor modification, by the introduction of terms for the maximum amount of UVR, and for summer precipitation and winter precipitation, to account for almost all the variation in skin reflectance. A further significant finding was that the effect of summer UVR seems to reach a threshold beyond which further adaptation is difficult.     

Adverse effects of ultraviolet radiation: a brief review

Solar ultraviolet radiation (UVR) has always been part of the environment of man. UVB is required for the conversion of 7-deoxycholesterol to vitamin D, which is critically important in the maintenance of healthy bones and research is making clear that it has other potential roles in maintenance of human health. Exposure to UVR, whether of solar or artificial origin, also carries potential risks to human health. UVR is a known carcinogen and excessive exposure-at least to solar radiation in sunlight-increases risk of cancer of the lip, basal cell, and squamous cell carcinoma of the skin and cutaneous melanoma, particularly in fair skin populations. There is also evidence that solar UVR increases risk of several diseases of the eye, including cortical cataract, some conjunctival neoplasms, and perhaps ocular melanoma. Solar UVR may also be involved in autoimmune and viral diseases although more research is needed in these areas. Artificial UVR from tanning beds, welding torches, and other sources, may contribute to the burden of disease from UVR. This brief review will assess the human evidence for adverse health effects from solar and artificial UVR and will attempt to assign a degree of certainty to the major disease-exposure relationships based on the weight of available scientific evidence.     

UV-A induces persistent genomic instability in human keratinocytes through an oxidative stress mechanism

Ultraviolet-A (UV-A, 320 to 400 nm) radiation comprises 95% of the solar ultraviolet radiation (UVR) reaching the earth's surface. It has been associated experimentally and epidemiologically with malignant melanoma. In this study we investigated whether UV-A radiation can induce a persistent, heritable hypermutability in mammalian cells similar to that observed following ionising radiation (IR). Using the immortalized human skin keratinocyte cell line HaCaT we found that UV-A radiation does lead to a continuing reduction in plating efficiency, an increased "spontaneous" mutant fraction, and an increase in micronucleus formation up to 21 d after initial exposure. Reversal of these effects using catalase may indicate a role for hydrogen peroxide in this phenomenon. These results add to the significance of UV-A radiation as a risk factor in skin carcinogenesis.     

The mechanisms and consequences of ultraviolet-induced immunosuppression

Exposure to ultraviolet radiation (UVR) can result in immune suppression to antigens encountered within a few days of the irradiation. The process leading to the down-regulation in immune responses is complex. It is initiated by several photoreceptors located in the skin surface, namely DNA, trans-urocanic acid and membrane components. The absorption of UVR by these chromophores then leads to the release of a wide range of mediators that can affect antigen presenting cells locally or systemically. The final steps include the generation of antigen-specific T cells capable of regulating immunity. The consequences of the UV-induced changes in the skin immune system for the control of skin cancers, infectious diseases including vaccination, and autoimmune diseases are considered. Finally, the effects of active vitamin D, synthesised in the epidermis following UVR, are discussed in the context of the skin immune response.     

UV and pigmentation: molecular mechanisms and social controversies

Ultraviolet radiation (UVR) is an essential risk factor for the development of premalignant skin lesions as well as of melanoma and non-melanoma skin cancer. UVR exerts many effects on the skin, including tanning, carcinogenesis, immunomodulation, and production of vitamin D. Vitamin D (vit D) is important in the maintenance of healthy bones as well as other purported beneficial effects, amongst which is the potential for reducing risk of malignancy--though oral supplementation is fully capable of maintaining systemic levels. The known medical harm from UV exposure relates primarily to cancer of the skin--the most common organ in man to be affected by cancer. In this review, we summarize the knowledge about the ultraviolet (UV) response in regards to inflammation, immunosuppression, carcinogenesis and the tanning response. We also discuss vit D and UV, as well as public health implications of tanning behavior and commercial interests related to the promotion of UV exposure. As the most ubiquitous human carcinogen, UVR exposure represents both a challenge and enormous opportunity in the realm of skin cancer prevention.     

Recent advances in urocanic acid photochemistry, photobiology and photoimmunology.

Urocanic acid (UCA), produced in the upper layers of mammalian skin, is a major absorber of ultraviolet radiation (UVR). Originally thought to be a 'natural sunscreen', studies conducted a quarter of a century ago proposed that UCA may be a chromophore for the immunosuppression that follows exposure to UVR. With its intriguing photochemistry, its role in immunosuppression and skin cancer development, and skin barrier function, UCA continues to be the subject of intense research effort. This review summarises the photochemical, photobiological and photoimmunological findings regarding UCA, published since 1998.     

The impact of skin colour on human photobiological responses

Terrestrial solar ultraviolet radiation (UVR) exerts both beneficial and adverse effects on human skin. Epidemiological studies show a lower incidence of skin cancer in people with pigmented skins compared to fair skins. This is attributed to photoprotection by epidermal melanin, as is the poorer vitamin D status of those with darker skins. We summarize a wide range of photobiological responses across different skin colours including DNA damage and immunosuppression. Some studies show the generally modest photoprotective properties of melanin, but others show little or no effect. DNA photodamage initiates non‐melanoma skin cancer and is reduced by a factor of about 3 in pigmented skin compared with white skin. This suggests that if such a modest reduction in DNA damage can result in the significantly lower skin cancer incidence in black skin, the use of sunscreen protection might be extremely beneficial for susceptible population. Many contradictory results may be explained by protocol differences, including differences in UVR spectra and exposure protocols. We recommend that skin type comparisons be done with solar‐simulated radiation and standard erythema doses or physical doses (J/m²) rather than those based solely on clinical endpoints such as minimal erythema dose (MED).     

Unravelling the insulin-like growth factor I-mediated photoprotection of the skin

Chronic exposure of human skin to solar ultraviolet radiation (UVR) induces a range of biological reactions which may directly or indirectly lead to the development of skin cancer. In order to overcome these damaging effects of UVR and to reduce photodamage, the skin’s endogenous defence system functions in concert with the various exogenous photoprotectors. Growth factors, particularly insulin-like growth factor-I (IGF-I), produced within the body as a result of cellular interaction in response to UVR demonstrates photoprotective properties in human skin. This review summarises the impact of UVR-induced photolesions on human skin, discusses various endogenous as well as exogenous approaches of photoprotection described to date and explains how IGF-I mediates UVR photoprotective responses at the cellular and mitochondrial level. Further, we describe the current interventions using growth factors and propose how the knowledge of the IGF-I photoprotection signalling cascades may direct the development of improved UVR protection and remedial strategies.     

4-Thiothymidine sensitization of DNA to UVA offers potential for a novel photochemotherapy

Photochemotherapy, in which ultraviolet radiation (UVR: 280-400 nm) or visible light is combined with a photosensitizing drug to produce a therapeutic effect that neither drug or radiation can achieve alone, is a proven therapeutic strategy for a number of non-malignant hyperproliferative skin conditions and various cancers. Examples are psoralen plus UVA (320-400 nm) radiation (PUVA) and photodynamic therapy (PDT). All existing photochemotherapies have drawbacks - for example the association of PUVA with the development of skin cancer, and pain that is often associated with PDT treatment of skin lesions. There is a clear need to develop alternative approaches that involve lower radiation doses and/or improved selectivity for target cells. In this review, we explore the possibility to address this need by exploiting thionucleoside-mediated DNA photosensitisation to low, non toxic doses of UVA radiation.     

Extremophiles: radiation resistance microbial reserves and therapeutic implications

Micro‐organisms with the ability to survive in extreme environmental conditions are known as ‘extremophiles’. Currently, extremophiles have caused a sensation in the biotechnology/pharmaceutical industries with their novel compounds, known as ‘extremolytes’. The potential applications of extremolytes are being investigated for human therapeutics including anticancer drugs, antioxidants, cell cycle‐blocking agents, anticholesteric drugs, etc. It is hypothesized that the majority of ultraviolet radiation (UVR)‐resistant micro‐organisms can be used to develop anticancer drugs to prevent skin damage from UVR. The metabolites from UVR‐resistant microbes are a great source of potential therapeutic applications in humans. This article aims to discuss the potentials of extremolytes along with their therapeutic implications of UVR extremophiles. The major challenges of therapeutic development using extremophiles are also discussed.     

Eumelanin and pheomelanin concentrations in human epidermis before and after UVB irradiation

Pheomelanin is widely thought to be causally related to susceptibility to the harmful effects of ultraviolet radiation: epidemiological studies show that those with a higher ratio of pheomelanin to eumelanin in hair have higher rates of melanoma, and work in mouse and cell culture shows that pheomelanin generates excess free radicals after UVR exposure. By contrast, based on measurements of eumelanin and pheomelanin in human skin, before and following irradiation, we now report that both pheomelanin and eumelanin are positively related to skin colour, and by inference, inversely with cancer susceptibility. The ratio of melanin classes is similar in people with widely different cancer rates and UVR sensitivity. Although our numbers are small, our results extend previous work in man, and lead us to speculate that factors other than the amount of pheomelanin may be important in determining UVR susceptibility in persons with red hair.     

Ultraviolet-radiation induced skin inflammation: dissecting the role of bioactive lipids

Acute exposure of human skin to the ultraviolet radiation (UVR) in sunlight results in the sunburn response. This is mediated in part by pro-inflammatory eicosanoids and other bioactive lipids, which are in turn produced via mechanisms including UVR-induction of oxidative stress, cell signalling and gene expression. Sunburn is a self-limiting inflammation offering a convenient and accessible system for the study of human cutaneous lipid metabolism. Recent lipidomic applications have revealed that a wider diversity of eicosanoids may be involved in the sunburn response than previously appreciated. This article reviews the effects of UVR on cutaneous lipids and examines the contribution of bioactive lipid mediators in the development of sunburn. Since human skin is an active site of polyunsaturated fatty acid (PUFA) metabolism, and these macronutrients can influence the production of eicosanoids/bioactive lipids, as well as modulate cell signalling, gene expression and oxidative stress, the application of PUFA as potential photoprotective agents is also considered.     

Molecular mechanisms of ultraviolet radiation-induced immunosuppression

Solar ultraviolet radiation (UVR) is well known for its immunosuppressive properties. UVR can suppress immune reactions both in a local and a systemic fashion. One of the major molecular mediators of photoimmunosuppression is UVR-induced DNA damage. In contrast to immunosuppressive drugs, UVR does not act in a general but antigen-specific fashion. This is due to the induction of regulatory T cells. Epidermal Langerhans cells harboring UVR-induced DNA damage appear to be essentially involved in the induction of these cells. Cytokines including interleukin (IL)-12, -18 and -23 exert the capacity to reduce UVR-induced DNA damage via induction of DNA repair. Accordingly, these cytokines prevent UVR-mediated immunosuppression. In contrast to IL-18, IL-12 and IL-23 can also inhibit the suppressive activity of regulatory T cells by a mechanism which still needs to be determined. Clarification of the molecular mechanisms underlying UVR-induced immunosuppression will help to develop new immunosuppressive therapeutic strategies by utilizing UVR-induced regulatory T cells for the treatment of immune-mediated diseases. In addition, these insights will contribute to a better understanding of photocarcinogenesis since suppression of the immune system by UVR essentially contributes to the induction of skin cancer.     

Cyclobutane pyrimidine dimer formation is a molecular trigger for solar-simulated ultraviolet radiation-induced suppression of memory immunity in humans.

We tested the hypothesis that DNA is a target for solar-simulated ultraviolet radiation (ssUVR)-induced suppression of the reactivation of memory immunity in humans. T4N5 liposomes contain the DNA repair enzyme T4 endonuclease V. This cleaves DNA at the site of ultraviolet radiation (UVR)-induced cyclobutane pyrimidine dimers (CPD), initiating DNA repair. It has previously been used to show that CPDs are a key molecular trigger for UVR-induced immunosuppression in mice. To determine whether CPD formation is involved in UVR immunosuppression in humans, nickel-allergic volunteers were irradiated with a range of doses of ssUVR. T4N5 or empty liposomes were then applied after irradiation. Nickel-induced recall immunity was assessed by reflectance spectrometry. T4N5 liposomes inhibited immunosuppression and prevented ssUVR from reducing the number of epidermal dendritic cells. T4N5 liposomes also reduced macrophage infiltration into irradiated epidermis. These studies show that enhanced removal of CPDs from human skin protects from immunosuppression, hence demonstrating that these photolesions are an important molecular event in ssUVR-induced immunosuppression in humans. CPDs also triggered loss of dendritic cells and infiltration by macrophages. It is possible that these changes to antigen presenting cells contribute to ssUVR induced suppression of recall immunity to nickel in humans.     

Ultraviolet radiation: effects on risks of prostate cancer and other internal cancers

Governmental and research agencies worldwide have strongly advocated sun avoidance strategies in an attempt to counter marked increases in skin cancer incidence. Concurrently, there are reports describing widespread Vitamin D3 deficiency. Because 1,25-dihydroxyvitamin D3, through interaction with the Vitamin D receptor, exerts pleiotrophic effects, such deficiency might be expected to have clinical consequences. Indeed, various reports indicate that exposure to ultraviolet radiation (UVR) exerts a protective effect on development of some common diseases including internal cancers and multiple sclerosis. We describe studies indicating that modest exposure reduces risk of prostate cancer. The effect of UVR is mediated by skin type; at lower levels of exposure a relative inability to effect skin pigmentation is protective presumably because it allows more efficient Vitamin D3 synthesis. Polymorphic variants in genes associated with pigmentation including melanocyte stimulating hormone receptor and tyrosinase are also associated with prostate cancer risk. Overall, though preliminary and requiring cautious interpretation, these data indicate that moderate UVR exposure together with characteristics linked with less effective tanning confer reduced prostate cancer risk. Clearly, it is important to define safe levels of UVR that do not result in increased risk of skin cancers such as malignant melanoma.     

Biological weighting function for xanthophyll de-epoxidation induced by ultraviolet radiation

The light-induced de-epoxidation of xanthophylls is an important photoprotective mechanism in plants and algae. Exposure to ultraviolet radiation (UVR, 280–400 nm) can change the extent of xanthophyll de-epoxidation, but different types of responses have been reported. The de-epoxidation of violaxanthin (V) to zeaxanthin (Z), via the intermediate antheraxanthin, during exposure to UVR and photosynthetically active radiation (PAR, 400–700 nm) was studied in the marine picoplankter Nannochloropsis gaditana (Eustigmatophyceae) Lubián. Exposures used a filtered xenon lamp, which gives PAR and UVR similar to natural proportions. Exposure to UVR plus PAR increased de-epoxidation compared with under PAR alone. In addition, de-epoxidation increased with the irradiance and with the inclusion of shorter wavelengths in the spectrum. The spectral dependence of light-induced de-epoxidation under UVR and PAR exposure was well described by a model of epoxidation state (EPS) employing a biological weighting function (BWF). This model fit measured EPS in eight spectral treatments using Schott long pass filters, with six intensities for each filter, with a R² = 0.90. The model predicts that 56% of violaxanthin is de-epoxidated, of which UVR can induce as much as 24%. The BWF for EPS was similar in shape to the BWF for UVR inhibition of photosynthetic carbon assimilation in N. gaditana but with about 22-fold lower effectiveness. These results demonstrate a connection between the presence of de-epoxidated Z and the inhibition under UVR exposures in N. gaditana . Nevertheless, they also indicate that de-epoxidation is insufficient to prevent UVR inhibition in this species.     

Coral Skeletons Defend against Ultraviolet Radiation

Background

Many coral reef organisms are photosynthetic or have evolved in tight symbiosis with photosynthetic symbionts. As such, the tissues of reef organisms are often exposed to intense solar radiation in clear tropical waters and have adapted to trap and harness photosynthetically active radiation (PAR). High levels of ultraviolet radiation (UVR) associated with sunlight, however, represent a potential problem in terms of tissue damage.

Methodology/Principal Findings

By measuring UVR and PAR reflectance from intact and ground bare coral skeletons we show that the property of calcium carbonate skeletons to absorb downwelling UVR to a significant extent, while reflecting PAR back to the overlying tissue, has biological advantages. We placed cnidarians on top of bare skeletons and a UVR reflective substrate and showed that under ambient UVR levels, UVR transmitted through the tissues of cnidarians placed on top of bare skeletons were four times lower compared to their counterparts placed on a UVR reflective white substrate. In accordance with the lower levels of UVR measured in cnidarians on top of coral skeletons, a similar drop in UVR damage to their DNA was detected. The skeletons emitted absorbed UVR as yellow fluorescence, which allows for safe dissipation of the otherwise harmful radiation.

Conclusions/Significance

Our study presents a novel defensive role for coral skeletons and reveals that the strong UVR absorbance by the skeleton can contribute to the ability of corals, and potentially other calcifiers, to thrive under UVR levels that are detrimental to most marine life.     

PHOTOSYNTHETIC INSENSITIVITY OF THE TERRESTRIAL CYANOBACTERIUM NOSTOC FLAGELLIFORME TO SOLAR UV RADIATION WHILE REHYDRATED OR DESICCATED1

Photosynthetic performance of the terrestrial cyanobacterium Nostoc flagelliforme (M. J. Berkeley et M. A. Curtis) Bornet et Flahault during rehydration and desiccation has been previously characterized, but little is known about the effects of solar UV radiation (280–400 nm) on this species. We investigated the photochemical activity during rehydration and subsequent desiccation while exposing the filamentous colonies to different solar radiation treatments. Photochemical activity could be reactivated by rehydration under full‐spectrum solar radiation, the species being insensitive to both ultraviolet‐A radiation (UVAR; 315–400 nm) and ultraviolet‐B radiation (UVBR). When the rehydrated colonies were exposed for desiccation, the effective PSII photochemical yield was inhibited by visible radiation (PAR) at the initial stage of water loss, then increased with further decrease in water content, and reached its highest value at the water content of 10%–30%. However, no significant difference was observed among the radiation treatments except for the moment when they were desiccated to critical water content of about 2%–3%. At such a critical water content, significant reduction by UVBR of the effective quantum yield was observed in the colonies that were previously rehydrated under indoor light [without ultraviolet radiation (UVR)], but not in those reactivated under scattered or direct solar radiation (with UVR), indicating that preexposure to UVR during rehydration led to higher resistance to UVR during desiccation. The photosynthetic CO₂ uptake by the desiccated colonies was enhanced by elevation of CO₂ but was not affected by both UVAR and UVBR. It increased with enhanced desiccation to reach the maximal values at water content of 40%–50%. The UV‐absorbing compounds and the colony sheath were suggested to play an important role in screening harmful UVR.     

The relationship between constitutive pigmentation and sensitivity to ultraviolet radiation induced erythema is dose-dependent

The relationship between skin colour and experimental exposure to ultraviolet radiation (UVR) B, with response measured as erythema was studied. Two reflectance methods were used to measure skin colour--tristimulus colorimetry using a Minolta instrument (summarized as the alpha characteristic angle) and the melanin index based on the Diastron reflectance instrument. As expected both measures are highly correlated (0.91). A dose-dependent relationship between skin colour measured as the alpha characteristic angle and UVR was established, with the gradient increasing from 0.99 at 119 mJ to 2.7 at 300 mJ, with the relevant standard errors being 0.39 and 0.47, respectively. Similarly, for the melanin index (where the scale goes in the opposite direction) the gradient differs between -0.49 for 119 mJ and -0.91 for 300 mJ, with the standard errors being 0.14 and 0.17 respectively. The proportion of variation explained is also greater at higher UVR challenge doses. Studies relating UVR sensitivity and pigmentation need to take account of the dose of UVR administered.