Ultraviolet Radiation Response Research Articles

Luminescent fiber UV detection.

Herein, a luminescent fiber device for detecting ultraviolet (UV) intensity, which comprises a UV probe and a photoelectric converter, is proposed. The UV probe consists of a glass tube filled with luminescent material, which can be used for the efficient radiation conversion of UV radiation to the visible spectral region. The luminescent material, Y2O2S:Eu3+, is mixed with polydimethylsiloxane (PDMS) to form the core of the UV probe. Subsequently, the UV radiation response of the luminescent fiber device is investigated; the experimental results demonstrate that the direction-independent UV detection can be realized by using this luminescent fiber UV detection device while UV light is radiated radially along the UV probe. In addition, since partial discharge (PD) is accompanied by UV radiation, we hope to develop a spectral PD detection scheme based on optical fiber technology, which can broaden the role of optical technology and optical fiber technology in the field of PD detection.

Weakened tanning ability is an important mechanism for evolutionary skin lightening in East Asians

The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude environments. East Asians are ideal populations for studying skin color evolution because of the complex environment of East Asia. Here, we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase (PAH) in light-skinned Han Chinese individuals. The intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males (P < 0.05). In vitro luciferase and transcription factor binding assays show that the ancestral allele of rs10778203 could bind to SMAD2 and has a significant enhancer activity for PAH. However, the derived T allele (the major allele in East Asians) of rs10778203 decreases the binding activity of transcription factors and enhancer activity. Meanwhile, the derived T allele of rs10778203 shows a weaker ultraviolet radiation response in A375 cells and zebrafish embryos. Furthermore, rs10778203 decreases melanin production in transgenic zebrafish embryos after ultraviolet B (UVB) treatment. Collectively, PAH is a potential pigmentation gene that regulates skin tanning ability. Natural selection has enriched the adaptive allele, resulting in weakened tanning ability in East Asians, suggesting a unique genetic mechanism for evolutionary skin lightening in East Asians.

Transcriptomic Effects of Acute Ultraviolet Radiation Exposure on Two Syntrichia Mosses.

Ultraviolet radiation (UVR) is a major environmental stressor for terrestrial plants. Here we investigated genetic responses to acute broadband UVR exposure in the highly desiccation-tolerant mosses Syntrichia caninervis and Syntrichia ruralis, using a comparative transcriptomics approach. We explored whether UVR protection is physiologically plastic and induced by UVR exposure, addressing the following questions: (1) What is the timeline of changes in the transcriptome with acute UVR exposure in these two species? (2) What genes are involved in the UVR response? and (3) How do the two species differ in their transcriptomic response to UVR? There were remarkable differences between the two species after 10 and 30 min of UVR exposure, including no overlap in significantly differentially abundant transcripts (DATs) after 10 min of UVR exposure and more than twice as many DATs for S. caninervis as there were for S. ruralis. Photosynthesis-related transcripts were involved in the response of S. ruralis to UVR, while membrane-related transcripts were indicated in the response of S. caninervis. In both species, transcripts involved in oxidative stress and those important for desiccation tolerance (such as late embryogenesis abundant genes and early light-inducible protein genes) were involved in response to UVR, suggesting possible roles in UVR tolerance and cross-talk with desiccation tolerance in these species. The results of this study suggest potential UVR-induced responses that may have roles outside of UVR tolerance, and that the response to URV is different in these two species, perhaps a reflection of adaptation to different environmental conditions.

Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response.

Genetic screens in Saccharomyces cerevisiae have allowed for the identification of many genes as sensors or effectors of DNA damage, typically by comparing the fitness of genetic mutants in the presence or absence of DNA-damaging treatments. However, these static screens overlook the dynamic nature of DNA damage response pathways, missing time-dependent or transient effects. Here, we examine gene dependencies in the dynamic response to ultraviolet radiation-induced DNA damage by integrating ultra-high-density arrays of 6144 diploid gene deletion mutants with high-frequency time-lapse imaging. We identify 494 ultraviolet radiation response genes which, in addition to recovering molecular pathways and protein complexes previously annotated to DNA damage repair, include components of the CCR4-NOT complex, tRNA wobble modification, autophagy, and, most unexpectedly, 153 nuclear-encoded mitochondrial genes. Notably, mitochondria-deficient strains present time-dependent insensitivity to ultraviolet radiation, posing impaired mitochondrial function as a protective factor in the ultraviolet radiation response.

Mitochondrial Sirtuins in Skin and Skin Cancers.

Mammalian sirtuins (SIRTs 1-7) are a family of NAD+-dependent deacetylases with distinct subcellular localization and biological functions that regulate various important cellular processes. Among these, SIRTs -3, -4 and -5 are located in the mitochondria and have been implicated in caloric restriction, oxidative stress, aging and various human diseases. Emerging evidence has found dysregulation of mitochondrial sirtuins in multiple dermatological conditions, including responses to ultraviolet radiation (UVR), suggesting their importance in maintaining skin health. In this review, we discuss the roles and implications of mitochondrial sirtuins in cutaneous cellular processes, and their emerging potential as a target for the management of skin diseases, including skin cancer. Among mitochondrial sirtuins, SIRT3 is the most studied and linked to multiple skin conditions and diseases (keratinocyte differentiation, wound healing, chronological aging, UVR and ozone response, systemic sclerosis, melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)). SIRT4 has been connected to keratinocyte differentiation, chronological aging, UVR response, alopecia, BCC and SCC. Further, SIRT5 has been associated with keratinocyte differentiation, melanoma, BCC and SCC. Overall, while there is compelling evidence for the involvement of mitochondrial sirtuins in skin, additional detailed studies are needed to understand their exact roles in skin and skin cancers.

UV radiation recruits CD4+GATA3+ and CD8+GATA3+ T cells while altering the lipid microenvironment following inflammatory resolution in human skin in vivo.

ObjectivesSolar ultraviolet radiation (UVR) has major adverse effects on human health. While the mechanisms responsible for induction of UVR‐induced inflammation are well‐documented, the mediation of its resolution and longer‐term adaptive homeostasis is unknown. Therefore, we examined the skin immune and lipid profile over time following UVR inflammation.MethodsTo investigate the self‐resolving events of UVR inflammation in vivo, human skin was exposed to a single pro‐inflammatory dose of UVR. Skin biopsies and suction blister fluid were taken at intervals up to 2 weeks post‐UVR. The immune infiltrate was quantified by immunohistochemistry, and lipid mediators were profiled by liquid chromatography/mass spectrometry.ResultsWe identified that cellular resolution events including switching of macrophage phenotype apply to human sunburn. However, UVR‐induced inflammation in humans involves a post‐resolution phase that differs from other experimental models. We demonstrate that 2 weeks after the initiating UVR stimulus, there is considerable immune activity with CD8+GATA3+ T cells maintained in human skin. Our results challenge the dogma of CD4+FOXP3+ T cells being the main effector CD4+ T‐cell population following UVR, with CD4+GATA3+ T cells the dominant phenotype. Furthermore, lipid mediators are elevated 14 days post‐UVR, demonstrating the skin lipid microenvironment does not revert to the tissue setting occurring prior to UVR exposure.ConclusionWe have identified for the first time that CD4+GATA3+ and CD8+GATA3+ T‐cell subpopulations are recruited to UVR‐inflamed human skin, demonstrating discrepancies between the adaptive UVR response in mice and humans. Future strategies to abrogate UVR effects may target these T‐cell subpopulations and also the persistent alteration of the lipid microenvironment post‐UVR.

Response of fluorescence morphs of the mesophotic coral Euphyllia paradivisa to ultra-violet radiation

Euphyllia paradivisa is a strictly mesophotic coral in the reefs of Eilat that displays a striking color polymorphism, attributed to fluorescent proteins (FPs). FPs, which are used as visual markers in biomedical research, have been suggested to serve as photoprotectors or as facilitators of photosynthesis in corals due to their ability to transform light. Solar radiation that penetrates the sea includes, among others, both vital photosynthetic active radiation (PAR) and ultra-violet radiation (UVR). Both types, at high intensities, are known to have negative effects on corals, ranging from cellular damage to changes in community structure. In the present study, fluorescence morphs of E. paradivisa were used to investigate UVR response in a mesophotic organism and to examine the phenomenon of fluorescence polymorphism. E. paradivisa, although able to survive in high-light environments, displayed several physiological and behavioral responses that indicated severe light and UVR stress. We suggest that high PAR and UVR are potential drivers behind the absence of this coral from shallow reefs. Moreover, we found no significant differences between the different fluorescence morphs’ responses and no evidence of either photoprotection or photosynthesis enhancement. We therefore suggest that FPs in mesophotic corals might have a different biological role than that previously hypothesized for shallow corals.

Negative phototactic response to UVR in three cosmopolitan rotifers: a video analysis approach

Ultraviolet radiation (UVR) is an environmental stressor in several ecosystems and can affect organisms’ survival and reproduction, and community structure. Rotifers cope with UVR stress adopting preventive behavioral and metabolic mechanisms. However, the demonstration of an immediate behavioral response in rotifers is missing. We investigated the short-term response of rotifers to UVR, by combining video analysis and movement ecology methods, in three common species: Brachionus calyciflorus, Keratella cochlearis, and Keratella quadrata. We recorded the behavior of B. calyciflorus (both sexes), K. quadrata, and K. cochlearis (females) exposed to white light, and to intermittent cycles of UVR (30:30 s). Individual trajectories were extracted from videos with open-source software. We found that B. calyciflorus females exposed to UVR exhibited strong negative phototaxis with increased swimming speed, and a weak positive phototaxis in males. Keratella cochlearis and K. quadrata showed a weaker response. Our study reveals a species-specific behavioral response to UVR in rotifers. Furthermore, we highlight how sexual dimorphism in B. calyciflorus does not only occur in morphology and movement, but also in behavioral traits. Our results help to understand zooplankton community dynamics by providing a mechanistic explanation of UVR response in one major zooplankton taxonomic group.

Radiosensitization by a Pyrrole-Imidazole Polyamide Through Interference with DNA Repair

Non-genotoxic small molecules that potentiate the effects of ionizing radiation in malignant cells could be used to augment radiotherapy for solid tumors. Pyrrole-imidazole (Py–Im) polyamides are synthetic non-genotoxic DNA minor groove-binding small molecules with programmable sequence specificity; binding to DNA induces allosteric changes that can interfere with protein-DNA interactions. We hypothesized that Py–Im polyamides can modulate the cellular response to ionizing radiation. The LNCaP and VCaP cell lines were used as model systems. Double (phosphorylated γ-H2AX) and single (XRCC1) DNA strand break foci were quantified by immunofluorescence. Cell viability was measured by xCELLIGence and PrestoBlue assays. Genomic fragmentation was measured by alkaline single cell gel electrophoresis. Gene expression changes were determined by RNA-sequencing. DNA ligase activity was assayed in vitro by gel-shift assay. A cell line expressing siRNA against DNA ligase 3 was used to determine if deficiency in this protein in vivo could potentiate cytotoxicity by a polyamide. Pre-treatment of cells with a Py-Im polyamide prior to exposure to ionizing radiation resulted in a delay in resolution of phosphorylated γ-H2AX foci, increase in XRCC1 foci, and reduced cellular replication potential. Polyamide treatment induced genes related to the ultraviolet radiation response. We observed that the polyamide is almost 10-fold more toxic to a cell line deficient in DNA ligase 3 as compared to the parental cell line. Alkaline single cell gel electrophoresis reveals that the polyamide induces genomic fragmentation in the ligase 3 deficient cell line but not the corresponding parental line. The polyamide interferes sequence-dependently with DNA ligation in vitro . These data support a model where a polyamide may interfere with repair of DNA strand breaks after ionizing radiation. We conclude that Py-Im polyamides may be further explored as sensitizers to genotoxic therapies.

Interference with DNA repair after ionizing radiation by a pyrrole-imidazole polyamide.

Pyrrole-imidazole (Py–Im) polyamides are synthetic non-genotoxic minor groove-binding small molecules. We hypothesized that Py–Im polyamides can modulate the cellular response to ionizing radiation. Pre-treatment of cells with a Py-Im polyamide prior to exposure to ionizing radiation resulted in a delay in resolution of phosphorylated γ-H2AX foci, increase in XRCC1 foci, and reduced cellular replication potential. RNA-sequencing of cell lines exposed to the polyamide showed induction of genes related to the ultraviolet radiation response. We observed that the polyamide is almost 10-fold more toxic to a cell line deficient in DNA ligase 3 as compared to the parental cell line. Alkaline single cell gel electrophoresis reveals that the polyamide induces genomic fragmentation in the ligase 3 deficient cell line but not the corresponding parental line. The polyamide interferes directly with DNA ligation in vitro. We conclude that Py-Im polyamides may be further explored as sensitizers to genotoxic therapies.

Mechanisms and prevention of UV-induced melanoma.

Melanoma is the deadliest form of skin cancer and its incidence is rising, creating a costly and significant clinical problem. Exposure to ultraviolet (UV) radiation, namely UVA (315-400nm) and UVB (280-315nm), is a major risk factor for melanoma development. Cumulative UV radiation exposure from sunlight or tanning beds contributes to UV-induced DNA damage, oxidative stress, and inflammation in the skin. A number of factors, including hair color, skin type, genetic background, location, and history of tanning, determine the skin's response to UV radiation. In melanocytes, dysregulation of this UV radiation response can lead to melanoma. Given the complex origins of melanoma, it is difficult to develop curative therapies and universally effective preventative strategies. Here, we describe and discuss the mechanisms of UV-induced skin damage responsible for inducing melanomagenesis, and explore options for therapeutic and preventative interventions.

Gene expression of a two-component regulatory system associated with sunscreen biosynthesis in the cyanobacterium Nostoc punctiforme ATCC 29133.

Long-wavelength ultraviolet radiation (UVA) can damage cells through photooxidative stress, leading to harmful photosensitized proteins and pigments in cyanobacteria. To mitigate damage, some cyanobacteria secrete the UVA-absorbing pigment scytonemin into their extracellular sheath. Comparative genomic analyses suggest that scytonemin biosynthesis is regulated by the two-component regulatory system (TCRS) proteins encoded by Npun_F1277 and Npun_F1278 in the cyanobacterium Nostoc punctiforme ATCC 29133. To understand the dynamics of these genes, their expression was measured following exposure to UVA, UVB, high visible (VIS) irradiance and oxidative stress for 20, 40 and 60 min. Overall, both genes had statistically similar patterns of expression for all four conditions and were generally upregulated, except for those exposed to UVB by 60 min and for the cells under oxidative stress. The greatest UVA response was an upregulation by 20 min, while the response to UVB was the most dramatic and persisted through 40 min. High VIS irradiance resulted in a modest upregulation, while oxidative stress caused a slight downregulation. Both genes were also found to occur on the same transcript. These results demonstrate that these genes are positively responding to several light-associated conditions, which suggests that this TCRS may regulate more than just scytonemin biosynthesis under UVA stress.

Cysteine-rich receptor-like kinase CRK5 as a regulator of growth, development, and ultraviolet radiation responses in Arabidopsis thaliana.

In plants, receptor-like protein kinases play essential roles in signal transduction by recognizing extracellular stimuli and activating the downstream signalling pathways. Cysteine-rich receptor-like kinases (CRKs) constitute a large subfamily of receptor-like protein kinases, with 44 members in Arabidopsis thaliana. They are distinguished by the novel C-X8-C-X2-C motif (DUF26) in the extracellular domains. One of them, CRK5, is an important component of the biochemical machinery involved in the regulation of essential physiological processes. Functional characterization of crk5 mutant plants showed their clear phenotype, manifested by impaired stomatal conductance and accelerated senescence. This phenotype correlated with accumulation of reactive oxygen species, higher foliar levels of ethylene and salicylic acid, and increased transcript abundance for genes associated with signalling pathways corresponding to these hormones. Moreover, the crk5 plants displayed enhanced cell death and oxidative damage in response to ultraviolet radiation. Complementation of CRK5 mutation managed to recover the wild-type phenotype, indicating an essential role of this gene in the regulation of growth, development, and acclimatory responses.

Solar ultraviolet radiation response of EBT2 Gafchromic, radiochromic film

Measurement of solar ultraviolet (UV) radiation is an important aspect of dosimetry for the improved knowledge of UV exposure and its associated health related issues. EBT2 Gafchromic film has been designed by its manufacturers as an improved tool for ionizing radiation dosimetry. The film is stated as exhibiting a significant reduction in UV response. However, results have shown that when exposed to UV from the ‘bottom side’ i.e. from the thick laminate side, the film exhibits a sensitivity to solar UV radiation which is both measurable and accurate for UV dosimetry. Films were irradiated in this position to known solar UV exposures and results are quantified showing a reproducibility of measurement to within ±7% (1 SD) when compared to calibrated UV meters. With an exposure of 20 J cm−2 broad spectrum solar UV, the films net OD change was found to be 0.248 OD ± 0.021 OD when analysing the results using the red channel region of an Epson V700 desktop scanner. This was compared to 0.0294 OD ± 0.0053 OD change with exposure to the same UV exposure from the top side. This means that solar UV dosimetry can be performed using EBT2 Gafchromic film utilizing the underside of the film for dosimetry. The main advantages of this film type for measurement of UV exposure is the visible colour change and thus easy analysis using a desktop scanner as well as its uniformity in response and its robust physical strength for use in outside exposure situations.

Multiple melanoma susceptibility factors function in an ultraviolet radiation response pathway in skin

Exposure to ultraviolet radiation (UVR) and the familial melanoma susceptibility gene p16 (CDKN2A) are among the major risk factors which have been identified to contribute to the development of melanoma, and also significantly contribute to squamous cell carcinoma. We have previously shown that UVR induces p16(CDKN2A) expression in melanoma and keratinocyte cell lines and human skin, but the regulatory mechanisms controlling this expression are unknown. To determine the mechanism by which UVR induces p16(CDKN2A) expression in melanocytes and keratinocytes in the epidermis. We have used an in vitro cell lines model of the UVR response in skin to assess the changes in p16(CDKN2A) expression and the signalling pathways regulating these changes, and validated these findings in whole human skin cultures. We show that UVR-induced ERK signalling, mediated by BRAF, regulates p16(CDKN2A) expression at the transcriptional, and possibly translational level. This study demonstrates the biological connection between the known melanoma genes p16 (CDKN2A) and BRAF in a normal physiological response to UVR in the skin, and highlights the importance of defects in this biological pathway to melanoma and squamous cell carcinoma development.

Ultraviolet radiation-induced upregulation of antimicrobial proteins in health and disease

This article reviews recent data on the expression, regulation and activation of antimicrobial peptides (AMP) in human skin, and considers their potential protective and pro-inflammatory roles following upregulation by ultraviolet radiation (UVR). Antimicrobial peptides are small peptides that are key components of the innate immune system, originally identified by their vital role in protecting the body-environment interface from infection. However, it has now become clear that AMP have more extensive actions, including the provision of pivotal links with the adaptive immune system. Moreover, aberrant AMP expression may contribute to immuno-modulated inflammatory dermatoses including psoriasis, eczema and the photoaggravated condition lupus erythematosus. Recent work has demonstrated the direct upregulation of AMP in healthy skin by cutaneous UVR exposure. This may serve to protect the skin from risks imposed by both the biophysical barrier-compromise and the immunosuppression that are attributable to UVR exposure. Furthermore, it is observed that UVR provokes upregulation of AMP in an atypical manner in the photosensitivity disorder polymorphic light eruption. Dysregulated UVR responses of these pro-inflammatory proteins may play a role in the pathogenesis of certain immune-mediated diseases caused or aggravated by sunlight.

Part II. Initial molecular and cellular characterization of high nitric oxide-adapted human tongue squamous cell carcinoma cell lines

It is not understood why some head and neck squamous cell carcinomas, despite having identical morphology, demonstrate different tumor aggressiveness, including radioresistance. High levels of the free radical nitric oxide (NO) and increased expression of the NO-producing enzyme nitric oxide synthase (NOS) have been implicated in tumor progression. We previously adapted three human tongue cancer cell lines to high NO (HNO) levels by gradually exposing them to increasing concentrations of an NO donor; the HNO cells grew faster than their corresponding untreated ("parent") cells, despite being morphologically identical. Herein we initially characterize the HNO cells and compare the biological properties of the HNO and parent cells. HNO/parent cell line pairs were analyzed for cell cycle distribution, DNA damage, X-ray and ultraviolet radiation response, and expression of key cellular enzymes, including NOS, p53, glutathione S-transferase-pi (GST-pi), apurinic/apyrimidinic endonuclease-1 (APE1), and checkpoint kinases (Chk1, Chk2). While some of these properties were cell line-specific, the HNO cells typically exhibited properties associated with a more aggressive behavior profile than the parent cells (greater S-phase percentage, radioresistance, and elevated expression of GST-pi/APE1/Chk1/Chk2). To correlate these findings with conditions in primary tumors, we examined the NOS, GST-pi, and APE1 expression in human tongue squamous cell carcinomas. A majority of the clinical samples exhibited elevated expression levels of these enzymes. Together, the results herein suggest cancer cells exposed to HNO levels can develop resistance to free radicals by upregulating protective mechanisms, such as GST-pi and APE1. These upregulated defense mechanisms may contribute to their aggressive expression profile.

Intraspecific comparisons reveal differences in the pattern of ultraviolet radiation responses in four maize ( Zea mays L.) varieties

Four maize ( Zea mays L.) varieties were examined for ultraviolet radiation-induced changes in leaf rolling, biomass, fluctuating leaf asymmetry and DNA damage. Short-term dose–response curves for each response were constructed and responses in each line compared. The four varieties each exhibited a different pattern of tolerance and reactivity, ranging from B73, which was tolerant in all four measures, to TS1, which was affected in DNA damage levels and leaf rolling but unaffected in biomass accumulation and fluctuating leaf asymmetry. The pattern of ultraviolet radiation responses allows us to narrow the possibilities for the source of the defect in reactive varieties. The four varieties tested include inbred parents that have been used to construct recombinant inbred lines and a variety that is found in the background of the engineered RescueMu transposon mutagenesis lines. These dose–response curves and variety comparisons provide the foundation for genetic dissection of the mechanisms of ultraviolet radiation responses in maize.

Ultraviolet radiation response to the physical properties of the reconstituted nucleohistone

The effect of UV irradiation on the reconstituted nucleohistone have been studied with reference to its (nucleohistone) changes in physical properties, after irradiation at different UV doses. The rate of fall of specific viscosity ratio of the reconstituted nucleohistone as a function of UV dose decreased gradually with the increasing histone to DNA weight ratio (r). This effect, was not observed when the histones remained dissociated from DNA, in high ionic strength (1.5 M NaCl). Histone-DNA complex (r=0.97) irradiated up to a dose of 3.6×10 4 J/m 2 had a stable melting temperature unlike free DNA where UV irradiation lowered the melting temperature and the heterogeneous melting profiles were observed. Rate of formaldehyde reaction, with DNA recovered from the irradiated complex, was slower than that with native DNA treated at the same dose. All this suggested that the effect of UV in the DNA of the nucleohistone was less, compared to that in free DNA.

RESISTANCE AND CROSS RESISTANCE OF ESCHERICHIA COLI S MUTANTS TO THE RADIOMIMETIC AGENT NITROFURAZONE.

Woody-Karrer, Pearl (Palo Alto Medical Research Foundation, Palo Alto, Calif.) and Joseph Greenberg. Resistance and cross resistance of Escherichia coli S mutants to the radiomimetic agent nitrofurazone. J. Bacteriol. 85:1208-1216. 1963.-Cross-resistance relationships are described for 73 mutants of Escherichia coli strain S selected in one step for resistance to nitrofurazone. The test agents included ultraviolet radiation, five radiomimetic compounds, and penicillin; 12 different types of mutants could be selected. Two of these were chemoresistant, three were identical to radioresistant types previously isolated by use of other radiomimetic agents, and seven represented previously unobserved radioresistant types. The majority of radioresistant strains did not respond to plating-medium reactivation after ultraviolet radiation, despite the ultraviolet radiation responses of several minority representative strains. The data presented indicate that radioresistance in E. coli S does not involve resistance to most toxic agents; on the other hand, cross resistance to radiomimetic compounds is not restricted to alkylating agents.