Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C/R24C/Tyr-NrasQ61K mice following neonatal UVR

To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4^R24C/R24C/Nras^Q61K mice topically with the T4 endonuclease V DNA repair enzyme (known as Dimericine) immediately prior to neonatal ultraviolet radiation (UVR) exposure, which has a powerful effect in exacerbating melanoma development in the mouse model. Dimericine has been shown to reduce the incidence of basal-cell and squamous cell carcinoma. Unexpectedly, we saw no difference in penetrance or age of onset of melanoma after neonatal UVR between Dimericine-treated and control animals, although the drug reduced DNA damage and cellular proliferation in the skin. Interestingly, epidermal melanocytes removed cyclobutane pyrimidine dimers (CPDs) more efficiently than surrounding keratinocytes. Our study indicates that neonatal UVR-initiated melanomas may be driven by mechanisms other than solely that of a large CPD load and/or their inefficient repair. This is further suggestive of different mechanisms by which UVR may enhance the transformation of keratinocytes and melanocytes.     

Various biological effects of solar radiation on skin and their mechanisms: implications for phototherapy

ABSTRACT

The skin protects our body from various external factors, such as chemical and physical stimuli, microorganisms, and sunlight. Sunlight is a representative environmental factor that considerably influences the physiological activity of our bodies. The molecular mechanisms and detrimental effects of ultraviolet rays (UVR) on skin have been thoroughly investigated. Chronic exposure to UVR generally causes skin damage and eventually induces wrinkle formation and reduced elasticity of the skin. Several studies have shown that infrared rays (IR) also lead to the breakdown of collagen fibers in the skin. However, several reports have demonstrated that the appropriate use of UVR or IR can have beneficial effects on skin-related diseases. Additionally, it has been revealed that visible light of different wavelengths has various biological effects on the skin. Interestingly, several recent studies have reported that photoreceptors are also expressed in the skin, similar to those in the eyes.

Based on these data, I discuss the various physiological effects of sunlight on the skin and provide insights on the use of phototherapy, which uses a specific wavelength of sunlight as a non-invasive method, to improve skin-related disorders.     

Isolate-specific effects of ultraviolet radiation on photosynthesis,growth and mycosporine-like amino acids in the microbial mat-forming cyanobacterium <Emphasis Type="Italic">Microcoleus </Emphasis><Emphasis Type="Italic">chthonoplastes</Emphasis>

Microcoleus chthonoplastes constitutes one of the dominant microorganisms in intertidal microbial mat communities. In the laboratory, the effects of repeated daily exposure to ultraviolet radiation (16:8 light:dark cycle) was investigated in unicyanobacterial cultures isolated from three different localities (Baltic Sea = WW6; North Sea = STO and Brittany = BRE). Photosynthesis and growth were measured in time series (12–15 days) while UV-absorbing mycosporine-like amino acids (MAAs) and cellular integrity were determined after 12 and 3 days exposure to three radiation treatments [PAR (22 μmol photon m⁻² s⁻¹) = P; PAR + UV-A (8 W m⁻²) = PA; PAR + UV-A + UV-B (0.4 W m⁻²) = PAB]. Isolate-specific responses to UVR were observed. The proximate response to radiation stress after 1-day treatment showed that isolate WW6 was the most sensitive to UVR. However, repeated exposure to radiation stress indicated that photosynthetic efficiency (F _v/F _m) of WW6 acclimated to UVR. Conversely, although photosynthesis in STO exhibited lower reduction in F _v/F _m during the first day, the values declined over time. The BRE isolate was the most tolerant to radiation stress with the lowest reduction in F _v/F _m sustained over time. While photosynthetic efficiencies of different isolates were able to acclimate to UVR, growth did not. The discrepancy seems to be due to the higher cell density used for photosynthesis compared to the growth measurement. Apparently, the cell density used for photosynthesis was not high enough to offer self-shading protection because cellular damage was also observed in those filaments under UVR. Most likely, the UVR acclimation of photosynthesis reflects predominantly the performance of the surviving cells within the filaments. Different strategies were observed in MAAs synthesis. Total MAAs content in WW6 was not significantly different between all the radiation treatments. In contrast, the additional fluence of UV-A and UV-B significantly increased MAAs synthesis and accumulation in STO while only UV-B fluence significantly increased MAAs content in BRE. Regardless of the dynamic photosynthetic recovery process and potential UV-protective functions of MAAs, cellular investigation showed that UV-B significantly contributed to an increased cell mortality in single filaments. In their natural mat habitat, M. chthonoplastes benefits from closely associated cyanobacteria which are highly UVR-tolerant due to the production of the extracellular UV-sunscreen scytonemin.     

Divergence in DNA photorepair efficiency among genotypes from contrasting UV radiation environments in nature

Populations of organisms routinely face abiotic selection pressures, and a central goal of evolutionary biology is to understand the mechanistic underpinnings of adaptive phenotypes. Ultraviolet radiation (UVR) is one of earth's most pervasive environmental stressors, potentially damaging DNA in any organism exposed to solar radiation. We explored mechanisms underlying differential survival following UVR exposure in genotypes of the water flea Daphnia melanica derived from natural ponds of differing UVR intensity. The UVR tolerance of a D. melanica genotype from a high‐UVR habitat depended on the presence of visible and UV‐A light wavelengths necessary for photoenzymatic repair of DNA damage, a repair pathway widely shared across the tree of life. We then measured the acquisition and repair of cyclobutane pyrimidine dimers, the primary form of UVR‐caused DNA damage, in D. melanica DNA following experimental UVR exposure. We demonstrate that genotypes from high‐UVR habitats repair DNA damage faster than genotypes from low‐UVR habitats in the presence of visible and UV‐A radiation necessary for photoenzymatic repair, but not in dark treatments. Because differences in repair rate only occurred in the presence of visible and UV‐A radiation, we conclude that differing rates of DNA repair, and therefore differential UVR tolerance, are a consequence of variation in photoenzymatic repair efficiency. We then rule out a simple gene expression hypothesis for the molecular basis of differing repair efficiency, as expression of the CPD photolyase gene photorepair did not differ among D. melanica lineages, in both the presence and absence of UVR.     

An integrated health risk assessment of indigenous children exposed to arsenic in Sonora,Mexico

Exposure to inorganic arsenic (InAs) through drinking water, even at low to moderate concentrations, is a global public health problem. The objectives of this study were to estimate the risk ratio (HQ), cancer risk (R), and DNA damage (comet assay) of children from three indigenous Yaqui populations located in southern Sonora, Mexico, who were exposed to InAs through drinking water. A cross-sectional study was employed, and analysis of InAs in water and urine was performed via HPLC/ICP-MS. InAs levels in drinking water from Pótam, Vícam, and Cócorit were 108.2, 36.0, and 6.2 μg/L^?1 respectively. Children from Pótam had arsenic concentrations in urine of 107.1 μg As L^?1 compared with 40.3 μg As L^?1 for the children of Cócorit. The HQ values for the children of Pótam, Vícam, and Cócorit were 16.64, 6.02, and 0.94, while the R values were 9.4E-04, 3.5E-04, and 5.7E-05, respectively. Children with the highest arsenic exposure had significantly increased DNA damage (OTM = 14.4 vs. 4.3) [p < 0.0005] which positively correlated with urinary arsenic levels (r = 0.56, p < 0.0001). In conclusion, children of Pótam and Vícam are at significant risk of developing chronic diseases and cancers associated with chronic exposure to this metalloid.     

Oxidant stress distressed

Summary

The range of photon energies in solar radiation and the diverse cell and molecular targets in skin allow for participation of oxygen radicals and oxidative stress at several levels in the development of skin cancer: DNA damage and mutation, membrane damage, and intracellular signalling. The intense UVA component of sunlight (315–400 nm) is of particular interest because of deep penetration, generation of oxidative damage and having a mutational spectrum which overlaps that of the more carcinogenic UVB (280–315 nm). Many UV-induced mutagenic and signalling events are now understood at the molecular level, and significant protection from UV carcinogenesis has been obtained with antioxidants in experimental animals. There is little evidence to suggest, however, that similar results have been achieved in humans although the converse effect has been established, of elevated skin cancer risk following simultaneous exposure to sunlight and precursors of the pro-oxidant paraquat. The present difficulty in translating these findings to prevent human skin cancer may arise from deficiencies in the models used and incomplete information about the specific responses of the target cells relevant to solar UV.     

UV effects on photosynthesis and DNA in propagules of three Antarctic seaweeds (<Emphasis Type="Italic">Adenocystis utricularis</Emphasis>, <Emphasis Type="Italic">Monostroma hariotii</Emphasis> and <Emphasis Type="Italic">Porphyra endiviifolium</Emphasis>)

Ozone depletion is highest during spring and summer in Antarctica, coinciding with the seasonal reproduction of most macroalgae. Propagules are the life-stage of an alga most susceptible to environmental perturbations therefore, reproductive cells of three intertidal macroalgal species Adenocystis utricularis (Bory) Skottsberg, Monostroma hariotii Gain, and Porphyra endiviifolium (A and E Gepp) Chamberlain were exposed to photosynthetically active radiation (PAR), PAR + UV-A and PAR + UV-A + UV-B radiation in the laboratory. During 1, 2, 4, and 8 h of exposure and after 48 h of recovery, photosynthetic efficiency, and DNA damage were determined. Saturation irradiance of freshly released propagules varied between 33 and 83 μmol photons m⁻² s⁻¹ with lowest values in P. endiviifolium and highest values in M. hariotii. Exposure to 22 μmol photons m⁻² s⁻¹ PAR significantly reduced photosynthetic efficiency in P. endiviifolium and M. hariotii, but not in A. utricularis. UV radiation (UVR) further decreased the photosynthetic efficiency in all species but all propagules recovered completely after 48 h. DNA damage was minimal or not existing. Repeated exposure of A. utricularis spores to 4 h of UVR daily did not show any acclimation of photosynthesis to UVR but fully recovered after 20 h. UVR effects on photosynthesis are shown to be species-specific. Among the tested species, A. utricularis propagules were the most light adapted. Propagules obviously possess good repair and protective mechanisms. Our study indicates that the applied UV dose has no long-lasting negative effects on the propagules, a precondition for the ecological success of macroalgal species in the intertidal.     

Thallus morphology and optical characteristics affect growth and DNA damage by UV radiation in juvenile Arctic Laminaria sporophytes

Growth of young sporophytes of the brown algae Laminaria digitata, L. saccharina and L. solidungula from Spitsbergen were measured in the laboratory after being exposed for 21 days to either photosynthetically active radiation (PAR=P) or to full light spectrum (PAR + UV-A + UV-B=PAB) using of cutoff glass filters. The plants were grown at 8±2°C and 16 h light : 8 h dark cycles with 6 h additional ultraviolet radiation (UVR) exposure in the middle of the light period. Growth was measured every 10 min using growth chambers with online video measuring technique. Tissue morphology and absorption spectra were measured in untreated young sporophytes while chlorophyll (Chl) a content and DNA damage were measured in treated thalli at the end of the experiment. In all species, growth rates were significantly higher in sporophytes exposed to P alone compared to sporophytes exposed to PAB. Tissue DNA damage is dependent on thallus thickness and absorption spectra characteristics of pigments and UV-absorbing compounds. In sporophytes exposed to UVR, energy demands for repair of DNA damage and synthesis of UV-absorbing compounds for protection effectively diverts photosynthate at the expense of growth. Photosynthetic pigment was not significantly different between treatments suggesting a capacity for acclimation to moderate UVR fluence. The general growth pattern in sporophytes exposed to P alone showed an increasing growth rate from the onset of light (0500–0900 hours) to a peak at the middle of the light phase (0900–1500 hours), a decline towards the end of the light phase (1500–2100 hours) and a minimum “low” growth in the dark (2100–0500 hours) relative to growth during the entire light phase. Under PAB, different growth patterns were observed such as growth compensation at night in L. digitata, delayed growth recovery in L. saccharina and minimal but continuous growth in L. solidungula. Growth as an integrative parameter of all physiological processes showed that the effect of UVR is correlated to the depth distribution of these species.     

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).     

COMBINED EFFECTS OF ULTRAVIOLET RADIATION AND TEMPERATURE ON MORPHOLOGY,PHOTOSYNTHESIS, AND DNA OF ARTHROSPIRA (SPIRULINA) PLATENSIS (CYANOPHYTA)1

Natural levels of solar UVR were shown to break and alter the spiral structure of Arthrospira (Spirulina) platensis (Nordst.) Gomont during winter. However, this phenomenon was not observed during summer at temperatures of ～30°C. Since little has been documented on the interactive effects of solar UV radiation (UVR; 280–400 nm) and temperature on cyanobacteria, the morphology, photosynthesis, and DNA damage of A. platensis were examined using two radiation treatments (PAR [400–700 nm] and PAB [PAR + UV‐A + UV‐B: 280–700]), three temperatures (15, 22, and 30°C), and three biomass concentrations (100, 160, and 240 mg dwt [dry weight] · L^?1). UVR caused a breakage of the spiral structure at 15°C and 22°C, but not at 30°C. High PAR levels also induced a significant breakage at 15°C and 22°C, but only at low biomass densities, and to lesser extent when compared with the PAB treatment. A. platensis was able to alter its spiral structure by increasing helix tightness at the highest temperature tested. The photochemical efficiency was depressed to undetectable levels at 15°C but was relatively high at 30°C even under the treatment with UVR in 8 h. At 30°C, UVR led to 93%–97% less DNA damage when compared with 15°C after 8 h of exposure. UV‐absorbing compounds were determined as negligible at all light and temperature combinations. The possible mechanisms for the temperature‐dependent effects of UVR on this organism are discussed in this paper.     

Acute Erythemal Ultraviolet Radiation Causes Systemic Immunosuppression in the Absence of Increased 25-Hydroxyvitamin D3 Levels in Male Mice

Vitamin D is synthesised by ultraviolet (UV) irradiation of skin and is hypothesized to be a direct mediator of the immunosuppression that occurs following UV radiation (UVR) exposure. Both UVR and vitamin D drive immune responses towards tolerance by ultimately increasing the suppressive activities of regulatory T cells. To examine a role for UVR-induced vitamin D, vitamin D₃-deficient mice were established by dietary vitamin D₃ restriction. In comparison to vitamin D₃-replete mice, vitamin D₃-deficient mice had significantly reduced serum levels of 25-hydroxyvitamin D₃ (25(OH)D₃, <20 nmol.L⁻¹) and 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃, <20 pmol.L⁻¹). Following either acute erythemal UVR, or chronic sub-erythemal UVR (8 exposures over 4 weeks) treatment, serum 25(OH)D₃ levels significantly increased in vitamin D₃-deficient female but not male mice. To determine if UVR-induced vitamin D was a mediator of UVR-induced systemic immunosuppression, responses were measured in mice that were able (female) or unable (male) to increase systemic levels of 25(OH)D₃ after UVR. Erythemal UVR (≥4 kJ/m²) suppressed contact hypersensitivity responses (T helper type-1 or -17), aspects of allergic airway disease (T helper type-2) and also the in vivo priming capacity of bone marrow-derived dendritic cells to a similar degree in female and male vitamin D₃-deficient mice. Thus, in male mice, UVR-induced 25(OH)D₃ is not essential for mediating the immunosuppressive effects of erythemal UVR.     

SENSITIVITY OF ANTARCTIC UROSPORA PENICILLIFORMIS (ULOTRICHALES,CHLOROPHYTA) TO ULTRAVIOLET RADIATION IS LIFE‐STAGE DEPENDENT1

The sensitivity of different life stages of the eulittoral green alga Urospora penicilliformis (Roth) Aresch. to ultraviolet radiation (UVR) was examined in the laboratory. Gametophytic filaments and propagules (zoospores and gametes) released from filaments were separately exposed to different fluence of radiation treatments consisting of PAR (P = 400–700 nm), PAR + ultraviolet A (UVA) (PA, UVA = 320–400 nm), and PAR + UVA + ultraviolet B (UVB) (PAB, UVB = 280–320 nm). Photophysiological indices (ETR_max, E_k, and α) derived from rapid light curves were measured in controls, while photosynthetic efficiency and amount of DNA lesions in terms of cyclobutane pyrimidine dimers (CPDs) were measured after exposure to radiation treatments and after recovery in low PAR; pigments of propagules were quantified after exposure treatment only. The photosynthetic conversion efficiency (α) and photosynthetic capacity (rETR_max) were higher in gametophytes compared with the propagules. The propagules were slightly more sensitive to UVB‐induced DNA damage; however, both life stages of the eulittoral inhabiting turf alga were not severely affected by the negative impacts of UVR. Exposure to a maximum of 8 h UVR caused mild effects on the photochemical efficiency of PSII and induced minimal DNA lesions in both the gametophytes and propagules. Pigment concentrations were not significantly different between PAR‐exposed and PAR + UVR–exposed propagules. Our data showed that U. penicilliformis from the Antarctic is rather insensitive to the applied UVR. This amphi‐equatorial species possesses different protective mechanisms that can cope with high UVR in cold‐temperate waters of both hemispheres and in polar regions under conditions of increasing UVR as a consequence of further reduction of stratospheric ozone.     

血清IL-6、IL-8、IgM抗体及T细胞亚群水平对新生儿先天性梅毒的诊断价值

目的:探讨血清白介素-6(IL-6)、白介素-8(IL-8)、IgM抗体及T细胞亚群对先天性梅毒新生儿的诊断价值。方法:选择2015年5月至2017年5月在我院进行临床治疗的先天性梅毒新生儿81例为观察组,另选同期来我院进行健康体检81例新生儿为对照组。比较两组患者血清IL-6、IL-8、T细胞亚群中CD~(3+)、CD~(4+)、CD~(8+)、CD~(4+)/CD~(8+)细胞及IgM抗体的阳性率。结果:治疗后,观察组血清IL-6、IL-8水平均明显高于对照组(P0.05),T细胞亚群中CD~(3+)、CD~(4+)、CD~(4+)/CD~(8+)明显低于对照组,而CD~(8+)T细胞比例高于对照组(P0.05)。19S-IgM-TP ELISA法检测出IgM的阳性率92.59%,明显高于TRUST法(74.07%)及TP-ELSA法(70.37%)(P0.05)。ROC曲线中,血清IL-8特异度为88.34%明显高于血清IL-6特异度81.48%、IgM抗体特异度60.13%、T细胞亚群特异度65.34%;IgM抗体的曲线面积88.91 cm~2明显大于IL-6的曲线面积45.09 cm~2、IL-8的曲线面积76.19 cm~2、T细胞亚群的曲线面积77.35 cm~2;T细胞亚群准备性67.89%明显高于IL-6准确性60.39%、IL-8准确性51.09%、IgM抗体准确性50.12;IgM抗体的灵敏度60.13%高于IL-6灵敏度59.19%、IL-8灵敏度42.35%、T细胞亚群灵敏度59.37%。具有比较意义(P0.05)。结论:血清IL-6、IL-8水平、T细胞亚群中CD~(3+)、CD~(4+)、CD~(8+)、CD~(4+)/CD~(8+)及IgM抗体阳性率是诊断先天性梅毒新生儿的重要指标。     

Effects of Power Frequency Electromagnetic Fields on Growth of Germinating Vicia faba L., the Broad Bean

Experimental investigations were carried out to evaluate the effect of continuous and delayed exposure of power frequency electromagnetic fields at 5, 50 and 100 μT on germinating Vicia faba seedlings as a model system. These studies included physical parameters (length and girth of primary roots, number as well as length of lateral roots and imbibition), major biochemical constituents (total sugar, protein, and fat) and activities of important housekeeping enzymes (amylases, proteases, and lipase) at 2, 4, and 8 days of growth. Also, mitotic index and rate of DNA synthesis were studied at day 8 of growth. There was no significant change in physical parameters and major biochemical constituents between control and experimental groups. Also, the comparison between the control and experimental group of seeds showed that α-amylase activity significantly decreased at 5, 50 and 100 μT on day 2 and 4 of growth. β-amylase and protease (37^○C & 50^○C) showed a significant decrease in activity on day 2 and 4 of growth at 100 μT, whereas activity of lipase significantly decreased only on day 2 of growth at 100 μT. At day 8 of growth, all enzyme activities reverted back to the same as control. Also, there was a significant increase in mitotic index as well as ³H-thymidine uptake at 100 μT delayed exposure on day 8. The present study suggests that exposure to power frequency electromagnetic fields up to 100 μT on germinating seedlings does not cause any permanent damage since the initial alteration under the magnetic fields in some important housekeeping enzymes involved in the onset of seed germination were returened to control values on day 8 of growth. Also, the growth of the germinated seedlings was found to be enhanced by the application of power frequency magnetic fields (100 μT) as evidenced by mitotic index and ³H-thymidine uptake.     

ADAPTATION OF A PSYCHROPHILIC FRESHWATER DINOFLAGELLATE TO ULTRAVIOLET RADIATION1

Little is known about the UV photobiology of psychrophilic dinoflagellates, particularly in freshwater systems. We addressed the life strategies of Borghiella dodgei Moestrup, Gert. Hansen et Daugbjerg to cope with ambient levels of ultraviolet radiation (UVR) under cold conditions. Several physiological parameters related to growth, metabolism, and UVR protection were determined for 4 d in UVR‐exposed and control cells by applying stable isotope analysis, spectrophotometry, and liquid chromatography–mass spectrometry (LC/MS). In UVR‐exposed cells, assimilation of ¹⁵N and ¹³C and content of chl a and carotenoids, specifically diatoxanthin with respect to dinoxanthin and diadinoxanthin, were increased; furthermore, catalase activity showed a cyclic pattern with a strong increase after UVR exposure but a rapid return to preexposure levels. Both in UVR‐exposed and control cells, no lipid peroxidation of galactolipids was observed. However, in UVR‐exposed cells, content of galactolipids was higher and linked to an increase in monogalactosyldiacylglycerols (MGDGs). We concluded that Borghiella's adaptation to UVR depended on a general metabolic enhancement and efficient scavenging of oxygen radicals to mitigate and counteract damage. While Borghiella seemed to be well adapted to ambient UVR, the interactive effects of higher temperature and UVR on psychrophilic species in front of climate change merit further investigation.     

Convenient and Efficient Syntheses of Oligodeoxyribonucleotides Containing O 6-(Carboxymethyl)Guanine and O 6-(4-Oxo-4-(3-Pyridyl)Butyl)Guanine

O ⁶-(carboxymethyl)guanine (O ⁶-CMG) and O ⁶-(4-oxo-4-(3-pyridyl)butyl)guanine (O ⁶-pobG) are toxic lesions formed in DNA following exposure to alkylating agents. O ⁶-CMG results from exposure to nitrosated glycine or nitrosated bile acid conjugates and may be associated with diets rich in red meat. O ⁶-pobG lesions are derived from alkylating agents found in tobacco smoke. Efficient syntheses of oligodeoxyribonucleotides (ODNs) containing O ⁶-CMG and O ⁶-pobG are described that involve nucleophilic displacement by the appropriate alcohol on a common synthetic ODN containing the reactive base 2-amino-6-methylsulfonylpurine. ODNs containing O ⁶-pobG and O ⁶-CMG were found to be good substrates for the S. pombe alkyltransferase-like protein Atl1.

[Supplemental materials are available for this article. Go to the publisher's online edition of Nucleosides, Nucleotides & Nucleic Acids to view the free supplemental file.]     

Narrow-band ultraviolet B (NB UV-B) exposures improve mood in healthy individuals differently depending on chronotype

ABSTRACT

The evening chronotype is associated with psychological symptoms such as depressed mood, while skin exposure to ultraviolet radiation (UVR) may affect mood and behavior through neural and humoral routes. This pilot study aimed to investigate the impact of whole-body narrow-band (NB) UV-B exposure on current mood state and circulating 25-hydroxyvitamin D3 (25(OH)D₃), interleukin-6 (IL-6), cortisol and β-endorphin (β-END) levels in healthy participants. Here, eleven healthy women received full-body NB UV-B exposures on four afternoons, and the chronotype was assessed with a shortened version of Horne and Östberg’s Morningness-Eveningness Questionnaire (MEQ). Perceived mood was evaluated using the Visual Analogue Scale (VAS), and serum 25(OH)D₃, IL-6, cortisol and β-END concentrations were monitored daily. Decreasing VAS values showed mood to improve significantly over the five days after the four suberythematous NB UV-B exposures (p = .038), and the more the circadian preference was inclined toward eveningness, the greater the improvement in the mood dimension of wellbeing (p = .021). Baseline mood state was correlated with baseline 25(OH)D₃ (r = ?0.54, 95% CI: ?0.86 to ?0.09) and with baseline cortisol (r = ?0.57, 95% CI: ?0.87 to ?0.04). During the NB UV-B exposures, 25(OH)D₃ increased significantly, as expected, and IL-6 declined significantly by ?0.35 (95% CI: ?0.69 to ?0.07) pg/mL from the initial values of 1.12 ± 0.66 pg/mL (p = .025). In conclusion, in our pilot study, NB UV-B exposure improved mood, especially among those with evening preference for their daily activities, as well as circulating 25(OH)D₃ levels, whereas circulating IL-6 levels decreased.

Abbreviations: UVR: Ultraviolet radiation; NB UV-B: narrow-band UV-B; VAS: Visual Analogue Scales; β-END: β-endorphin; IL-6: Interleukin-6     

Role of nucleotide excision repair deficiency in intestinal tumorigenesis in multiple intestinal neoplasia (Min) mice

Mice deficient in the Xeroderma pigmentosum group A (Xpa) gene are defective in nucleotide excision repair (NER) and highly susceptible to skin carcinogenesis after dermal exposure to UV light or chemicals. Min (multiple intestinal neoplasia) mice, heterozygous for a germline nonsense mutation in the tumor suppressor gene adenomatous polyposis coli (Apc), develop intestinal tumors spontaneously and show additional intestinal tumors after exposure to the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). In this study, we investigated the impact of loss of XPA function on PhIP-induced intestinal tumorigenesis in F1 offspring of Min/+ (Apc^+/−) mice crossed with Xpa gene-deficient mice. Apc^+/− mice lacking both alleles of Xpa had higher susceptibility towards toxicity of PhIP, higher levels of PhIP–DNA adducts in the middle and distal small intestines, as well as in liver, and a higher number of small intestinal tumors at 11 weeks, compared with Apc^+/− mice with one or two intact Xpa alleles. Localization of tumors was not affected, being highest in middle and distal small intestines in all genotypes. At 11 weeks of age, the number of spontaneous intestinal tumors was not significantly increased by homozygous loss of Xpa, but untreated Apc^+/−/Xpa^−/− mice had significantly shorter life-spans than their XPA-proficient littermates. Heterozygous loss of Xpa did not affect any of the measured end points. In conclusion, the Xpa gene and the NER pathway are involved in repair of bulky PhIP–DNA adducts in the intestines and the liver, and most probably of DNA lesions leading to spontaneous intestinal tumors. These results confirm a role of the NER pathway also in protection against cancer in internal organs, additional to its well-known importance in protection against skin cancer. An effect of Apc^+/− on adduct levels, additional to that of Xpa^−/−, indicates that the truncated APC protein may affect a repair pathway other than NER.