Low-dose UVA Research Articles

Impact of low-dose UV-A in Caenorhabditis elegans during candidate bacterial infections.

Ultraviolet radiation is a non-ionizing radiation produced by longer wavelength energy sources with lower frequency and is categorized into UV-A, UV-B, and UV-C. Minimal exposure to this radiation has several health benefits, which include treating microbial contaminations and skin therapies. However, the antimicrobial action of low-dose UV-A during pathogenic bacterial infections is still unrevealed. In this study, the impact of low-dose UV-A as pre- or post-treatment using the model organism, Caenorhabditis elegans with candidate pathogens (Acinetobacter baumannii and Staphylococcus aureus) mediated infections was investigated. The results indicated enrichment of metabolites, reduced level of antioxidants, increased expression of dopamine biosynthesis and transportation, and decrease in serotonin biosynthesis when the organism was exposed to low-dose UV-A for 5 min. This, in turn, elevated the expression of candidate regulatory proteins involved in lifespan determination, innate immunity, and cAMP-response element binding protein (CREB), which appear to increase the lifespan and brood size of C. elegans during A. baumannii and S. aureus infections. The findings suggested that the low-dose UV-A treatment during A. baumannii and S. aureus infections prolonged the lifespan and increased the egg-laying capacity of C. elegans.

1175 Impact of low dose UVA radiation on UVB radiation-induced DNA damage and skin carcinogenesis

1175 Impact of low dose UVA radiation on UVB radiation-induced DNA damage and skin carcinogenesis

Low Dose UVA-1 Treatment in Atopic Dermatitis: Does Treatment Response Depend on Age and Gender?

Low Dose UVA-1 Treatment in Atopic Dermatitis: Does Treatment Response Depend on Age and Gender?

Role of Pel and Psl polysaccharides in the response of Pseudomonas aeruginosa to environmental challenges: oxidative stress agents (UVA, H2O2, sodium hypochlorite) and its competitor Staphylococcus aureus.

Pseudomonas aeruginosa is a versatile bacterium capable of adapting to a wide range of stress factors, including solar UVA radiation (400-315 nm). High UVA doses produce lethal effects due to the action of reactive oxygen species. Sublethal UVA doses also induces oxidative damage, but, in addition, it triggers a variety of adaptive responses, including the overexpression of pelA and pslA genes in P. aeruginosa. These genes encode the synthesis of Pel and Psl, which are essential polysaccharides in biofilm formation. The present study analysed the role of Pel and Psl in the adaptive responses generated by exposure to low UVA doses, and their importance in the response to lethal doses of UVA, hydrogen peroxide (H2O2), and sodium hypochlorite, in both planktonic cells and submerged and air-liquid interface (ALI) biofilms. It also studied the roles of Pel and Psl in P. aeruginosa-Staphylococcus aureus interaction. The results demonstrate that the capacity of sublethal UVA exposure to increase cell hydrophobicity and cell attachment and generate cross-protection phenomena in P. aeruginosa depends on the presence of Pel and Psl. The study also shows that Pel and Psl have a key role in the tolerance to lethal doses of UVA radiation, sodium hypochlorite and H2O2, in both biofilms and planktonic cells. Finally, co-culture assays showed total inhibition of S. aureus growth in presence of P. aeruginosa. This phenomenon depends, at least in part, on the simultaneous presence of Pel and Psl in planktonic cells and biofilms, suggesting a relevant role of these polysaccharides in the interaction between these species.

Photosensitization of human skin fibroblasts by vemurafenib promotes pleiotropic effects on membrane-enclosed organelles and apoptosis.

Vemurafenib (VB), a BRAF inhibitor and a first-line treatment for unresectable or metastatic melanoma, is strongly phototoxic towards normal skin cells. Herein, we show that in cultured HS 68 human diploid dermal fibroblasts, low concentrations of VB suffice to promote photosensitization to low doses of UVA (∼ 5J/cm2), as evidenced by a significant decrease in cell viability. In contrast to data obtained in chemico our results support a role for ROS (reactive oxygen species). Indeed, peroxidation of cellular lipids was observed which could be alleviated by the lipophilic antioxidant BHT (2,6-di-tert-butyl-4-methylphenol). Using in vivo confocal laser scanning microscopy and vital fluorescent probes it was shown at the single cell level that the plasma membrane and lipid-rich organelles, namely mitochondria, endoplasmic reticulum, and lysosomes, as well as actin filaments, were severely damaged by the UVA-induced VB-photosensitization. Finally, we showed that mitochondrial impairment was concurrent with caspase 3/7 activation and cell death by apoptosis.

The effect of daily UVA phototherapy for 2 weeks on clinic and 24-h blood pressure in individuals with mild hypertension

Latitude and season determine exposure to ultraviolet radiation and correlate with population blood pressure. Evidence for Vitamin D causing this relationship is inconsistent, and temperature changes are only partly responsible for BP variation. In healthy individuals, a single irradiation with 20 J/cm2 UVA mobilises NO from cutaneous stores to the circulation, causes arterial vasodilatation, and elicits a transient fall in BP. We, therefore, tested whether low-dose daily UVA phototherapy might be an effective treatment for mild hypertension. 13 patients with untreated high-normal or stage 1 hypertension (BP 130-159/85-99 mm Hg), confirmed by 24-h ambulatory blood pressure (ABP), were recruited. Using home phototherapy lamps they were either exposed to 5 J/cm2 full body UVA (320–410 nm) radiation each day for 14 days, or sham-irradiated with lamps filtered to exclude wavelengths <500 nm. After a washout period of 3 ± 1 week, the alternate irradiation was delivered. 24-h ABP was measured on day 0 before either irradiation sequence and on day 14. Clinic BP was recorded on day 0, and within 90 min of irradiation on day 14. There was no effect on 24-h ABP following UVA irradiation. Clinic BP shortly after irradiation fell with UVA (−8.0 ± 2.9/−3.8 ± 1.1 mm Hg p = 0.034/0.029) but not sham irradiation (1.1 ± 3.0/0.9 ± 1.5 mm Hg). Once daily low-dose UVA does not control mildly elevated BP although it produces a transient fall shortly after irradiation. More frequent exposure to UVA might be effective. Alternatively, UVB, which photo-releases more NO from skin, could be tried.

More Than Skin Deep - the Effects of Ultraviolet Radiation on Cathepsin K and Progerin Expression in Cultured Dermal Fibroblasts.

IntroductionPhotoaging is a premature skin aging developing secondarily to the excessive exposure to ultraviolet radiation. Due to its complexity, an exact mechanism of photoaging has not been found yet; however, recent research has shown two new emerging players in this process – cathepsin K and progerin.AimTo evaluate how different wavelengths of ultraviolet radiation (UVA, narrowband UVB and broadband UVB) influence cathepsin K and progerin protein and mRNA expression in dermal cultured fibroblasts.Materials and MethodsPrimary human dermal fibroblasts (Detroit 551, ATCC CCL-110) were cultured and irradiated with UVA, narrowband UVB (UVBnb) and broadband UVB (UVBwb). Fibroblasts were irradiated with 2 protocols: single high-dose exposure to UVR with protein/mRNA extraction immediately after exposure, 24 h after exposure and 48 h after exposure, and repeated (0 h, 24 h and 48 h) low-dose exposure to UVR with protein/mRNA extraction 48 h after first exposure.ResultsSingle high doses of UVA, UVBwb and UVBnb resulted in decreased expression of cathepsin K and progerin protein/mRNA in all subsequent time points. Repeated exposure to low doses of UVA results in significant increase of progerin mRNA and significant decrease of progerin protein after 48 h, but repeated exposure to UVBwb and UVBnb resulted in decreased progerin mRNA and protein expression. Repeated exposure to UVA, UVBwb and UVBnb resulted in decreased cathepsin K protein and mRNA expression.ConclusionThe results suggest that there could be another progerin/cathepsin K regulatory pathway, which has not been described yet. Being contradictory with previous research, the influence of ultraviolet radiation on progerin and cathepsin K needs to be further elucidated.

Vitamin C prevents epidermal damage induced by PM-associated pollutants and UVA1 combined exposure.

Particulate matter is suspected to be substantially involved in pollution-induced health concerns. In fact, ultrafine particles (UFPs) contain polycyclic aromatic hydrocarbons (PAHs) known as mutagenic, cytotoxic and sometimes phototoxic. Since UFPs reach blood circulation from lung alveoli, deep skin is very likely contaminated by PAHs coming from either skin surface or blood. As photoreactive, benzo(a)pyrene (BaP) or indenopyrene (IcdP) is involved in the interplay between pollution and sunlight. In order to better characterize this process, experiments were carried out on reconstructed human epidermis (RHE) in a protocol mimicking realistic exposure. Concentrations of PAHs comparable to those generally reported in blood were used together with chronic irradiation to low dose UVA1. On a histological level, damaged cells mainly accumulated in a suprabasal situation, thus reducing living epidermis thickness. Stress markers such as IL1-α or MMP3 secretion increased, and surprisingly, the histological position of Transglutaminase-1 within epidermis was disturbed, whereas position of other differentiation markers (keratin-10, filaggrin, loricrin) remained unchanged. When vitamin C was added in culture medium, a very significant protection involving all markers was noticed. In conclusion, we provide here a model of interest to understand the epidermal deleterious consequences of pollution and to select efficient protective compounds.

UVA Radiation Enhances Lomefloxacin-Mediated Cytotoxic, Growth-Inhibitory and Pro-Apoptotic Effect in Human Melanoma Cells through Excessive Reactive Oxygen Species Generation.

Melanoma, the most dangerous type of cutaneous neoplasia, contributes to about 75% of all skin cancer-related deaths. Thus, searching for new melanoma treatment options is an important field of study. The current study was designed to assess whether the condition of mild and low-dose UVA radiation augments the lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effect of the drug in melanoma cancer cells through excessive oxidative stress generation. C32 amelanotic and COLO829 melanotic (BRAF-mutant) melanoma cell lines were used as an experimental model system. The combined exposure of cells to both lomefloxacin and UVA irradiation caused higher alterations of redox signalling pathways, as shown by intracellular reactive oxygen species overproduction and endogenous glutathione depletion when compared to non-irradiated but lomefloxacin-treated melanoma cells. The obtained results also showed that lomefloxacin decreased both C32 and COLO829 cells’ viability in a concentration-dependent manner. This effect significantly intensified when melanoma cells were exposed to UVA irradiation and the drug. For melanoma cells exposed to lomefloxacin or lomefloxacin co-treatment with UVA irradiation, the concentrations of the drug that decreased the cells’ viability by 50% (EC50) were found to be 0.97, 0.17, 1.01, 0.18 mM, respectively. Moreover, we found that the redox imbalance, mitochondrial membrane potential breakdown, induction of DNA fragmentation, and changes in the melanoma cells’ cell cycle distribution (including G2/M, S as well as Sub-G1-phase blockade) were lomefloxacin in a dose-dependent manner and were significantly augmented by UVA radiation. This is the first experimental work that assesses the impact of excessive reactive oxygen species generation upon UVA radiation exposure on lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effects towards human melanoma cells, indicating the possibility of the usage of this drug in the photochemotherapy of malignant melanoma as an innovative medical treatment option which could improve the effectiveness of therapy. The obtained results also revealed that the redox imbalance intensification mediated by the phototoxic potential of fluoroquinolones may be considered as a more efficient treatment model of malignant melanoma and may constitute the basis for the development of new compounds with a high ability to excessive oxidative stress generation upon UVA radiation in cancer cells.

Vemurafenib-related photosensitivity.

Increased photosensitivity is a common cutaneous adverse effect associated with the BRAF inhibitor vemurafenib. Clinically, it presents as an immediate sensation of heat and edematous erythema during sun exposure, as well as a sunburn reaction in terms of a late reaction. Phototesting has shown that the UVA range (320nm to 400 nm), triggers both the immediate and the late reaction. In terms of pathogenesis, photochemical studies have suggested that exposure of vemurafenib to UVA radiation produces an UVA-absorbing photoproduct. In vitro studies on various cell models have also demonstrated that the phototoxic effects of vemurafenib are exclusively caused by UVA irradiation. This latter mechanism is probably responsible for the photosensitivity clinically observed in patients receiving vemurafenib. In addition, vemurafenib is able to inhibit ferrochelatase. The resulting increase in protoporphyrinIX has also been observed in some human studies involving the drug. However, it is yet unproven whether porphyrins actually contribute to the immediate skin reactions seen in individuals on vemurafenib, even though the clinical presentation is similar to that found in erythropoietic protoporphyria with a comparable pathomechanism. Other BRAF inhibitors, such as dabrafenib and encorafenib, are associated with significantly lower photosensitivity. It is essential that patients treated with vemurafenib are informed about immediate and delayed reactions potentially caused even by low doses of UVA. This includes counseling on photoprotective measures.

Photorheology of bioadhesive dendrimer polycaprolactone composites

Toxicity, low adhesion strength, and complexity of application are the major challenges that prevent utilization of synthetic surgical adhesives. To address this challenge, a platform of fully synthetic UVA curing bioadhesive is evaluated on the binary composites consisting of polyamidoamine (PAMAM) grafted with aryl-diazirine (PAMAM-g-diazirine, PDz) and multi-arm polycaprolactone triols (PCLT). PCLT is chosen as a bioresorbable polymer matrix that serves as a plasticizer for the viscous PDz. Upon low dose UVA light, grafted diazirine converts to reactive carbenes that crosslink by covalent insertion. Rheological investigation created G″ vs. G′ vector maps of the liquid-to-solid transition, allowing comparison of PDz/PCLT ratio, PCLT molar mass, and type of plasticizer. The vector maps reveal crosslinking kinetics are dependent on the PCLT concentration within the composite, while the molar mass of liquid PCLT does not affect the crosslinking kinetics. Liquid PDz/PCLT composite adheres to dry substrates as well as hydrated soft tissue mimics. Infrared spectroscopy provides an insight into the crosslinking mechanism where UVA-generated carbenes covalently insert into proximate polymer chains mainly on –O–H sites. Carbene-induced intermolecular locking transforms the material from liquid to elastomeric composite polymer matrix in less than 10 J per sq. cm of UVA exposure.

Interventions for morphea.

Interventions for morphea.

ATR/Chk1 Pathway is Activated by Oxidative Stress in Response to UVA Light in Human Xeroderma Pigmentosum Variant Cells.

The crucial role of DNA polymerase eta in protecting against sunlight-induced tumors is evidenced in Xeroderma Pigmentosum Variant (XP-V) patients, who carry mutations in this protein and present increased frequency of skin cancer. XP-V cellular phenotypes may be aggravated if proteins of DNA damage response (DDR) pathway are blocked, as widely demonstrated by experiments with UVC light and caffeine. However, little is known about the participation of DDR in XP-V cells exposed to UVA light, the wavelengths patients are mostly exposed. Here, we demonstrate the participation of ATR kinase in protecting XP-V cells after receiving low UVA doses using a specific inhibitor, with a remarkable increase in sensitivity and γH2AX signaling. Corroborating ATR participation in UVA-DDR, a significant increase in Chk1 protein phosphorylation, as well as S-phase cell cycle arrest, is also observed. Moreover, the participation of oxidative stress is supported by the antioxidant action of N-acetylcysteine (NAC), which significantly protects XP-V cells from UVA light, even in the presence of the ATR inhibitor. These findings indicate that the ATR/Chk1 pathway is activated to control UVA-induced oxidatively generated DNA damage and emphasizes the role of ATR kinase as a mediator of genomic stability in pol eta defective cells.

Early-stage photodegradation of aromatic poly(urethane-urea) elastomers

The photooxidative stability of an aromatic segmented poly(urethane-urea) (PUU) elastomer, stabilised with a range of carbon black fillers, was assessed after very low UVA doses as a means to identify components that are highly susceptible to UV degradation, and suggest better design of such materials. Fourier-transform infrared (FTIR) analysis indicated rapid degradation of the urea bonds in the hard segments, followed by chain scission and photo-Fries reaction of the urethane linkages. In the soft segments, the oxidation of the original ether groups resulted in the formation of large amounts of ester groups, while some crosslinking of the ether groups was also evident. Carbon black provided moderate protection against degradation, with the smallest-sized particles being the most effective. Protection was evidenced by reduced surface cracking as well as an increased resistance to chemical changes in both the soft segments and hard segments. Even so, significant degradation was still evident at low UV doses suggesting that further stabilisation is required to increase the UV durability of these elastomers and improve their long-term performance.

Do UV-A radiation and blue light during growth prime leaves to cope with acute high light in photoreceptor mutants of Arabidopsis thaliana?

We studied how plants acclimated to growing conditions that included combinations of blue light (BL) and ultraviolet (UV)-A radiation, and whether their growing environment affected their photosynthetic capacity during and after a brief period of acute high light (as might happen during an under-canopy sunfleck). Arabidopsis thaliana Landsberg erecta wild-type were compared with mutants lacking functional blue light and UV photoreceptors: phototropin 1, cryptochromes (CRY1 and CRY2) and UV RESISTANT LOCUS 8 (uvr8). This was achieved using light-emitting-diode (LED) lamps in a controlled environment to create treatments with or without BL, in a split-plot design with or without UV-A radiation. We compared the accumulation of phenolic compounds under growth conditions and after exposure to 30 min of high light at the end of the experiment (46 days), and likewise measured the operational efficiency of photosystem II (ϕPSII, a proxy for photosynthetic performance) and dark-adapted maximum quantum yield (Fv /Fm to assess PSII damage). Our results indicate that cryptochromes are the main photoreceptors regulating phenolic compound accumulation in response to BL and UV-A radiation, and a lack of functional cryptochromes impairs photosynthetic performance under high light. Our findings also reveal a role for UVR8 in accumulating flavonoids in response to a low UV-A dose. Interestingly, phototropin 1 partially mediated constitutive accumulation of phenolic compounds in the absence of BL. Low-irradiance BL and UV-A did not improve ϕPSII and Fv /Fm upon our acute high-light treatment; however, CRYs played an important role in ameliorating high-light stress.

Exposure to low doses of UVA increases biofilm formation in Pseudomonas aeruginosa

The establishment of bacterial biofilms on abiotic surfaces is a complex process regulated by multiple genetic regulators and environmental factors which are able to modulate the passage of planktonic cells to a sessile state. Solar ultraviolet-A radiation (UVA, 315-400) is one of the main environmental stress factors that bacteria must face at the Earth´s surface. The deleterious effects of UVA are mainly due to oxidative damage. This paper reports that exposure to low UVA doses promotes biofilm formation in three prototypical strains of Pseudomonas aeruginosa, a relevant opportunistic human pathogen. It demonstrates that exposure of planktonic cells to sublethal doses of UVA can increase cell surface hydrophobicity and swimming motility, two parameters known to favor cell adhesion. These results suggest that UVA radiation acts, at least in part, by promoting the first stages of biofilm development.

Establishment of Photoaging In Vitro by Repetitive UVA Irradiation: Induction of Characteristic Markers of Senescence and its Prevention by PAPLAL with Potent Catalase Activity.

To understand a role of UVA radiation in photoaging of the skin, we established a model of photoaging cells using cultured human dermal fibroblasts. Repeated low-dose UVA radiation for 10 consecutive days induced senescence in fibroblasts, characterized with (1) increased level of senescence-associated β-galactosidase, (2) flattened large cell shape, (3) accumulation of reactive oxygen species, (4) yellowish coloration and (5) expression of p16. These were also observed in chronologically aged fibroblasts (doubling times >20), whereas none of these were detected in young cells (doubling times <10). Collectively, we propose that fibroblasts exposed to repetitive UVA radiation may be a good model of aged cells to study the mechanism of aging and photoaging and further to search for novel agents preventing cellular senescence. In addition, H2 O2 was produced in the culture medium by a single low dose of UVA irradiation. Further, PAPLAL, a nanoparticle of platinum and palladium having potent catalase-like activity, significantly delayed the onset of H2 O2 -induced cell senescence. The present study strongly indicates that repetitive short-term UVA irradiation induces aging of cells possibly via H2 O2 and may be suppressed by potent anti-H2 O2 agents.

The effects of phototherapy and melanocytes on keratinocytes.

Phototherapy is widely used in the treatment of vitiligo. Previous studies have focused on the effects of ultraviolet (UV) radiation on melanocytes; however, the biological effects of phototherapy and melanocytes on keratinocytes remain to be elucidated. To investigate and assess the effects of clinically doses of broad band (BB)-UVA, narrow band (NB)-UVB and melanocytes on human keratinocytes in vitro, clinical doses of BB-UVA or NB-UVB radiation and human melanoma cell A375 co-culture were performed as stress divisors to HaCaT cells. Cell proliferation, expression of protease-activated receptor-2 (PAR-2) and nuclear factor E2-related factor 2 mRNA, lipid peroxidation and intracellular antioxidant level of keratinocytes were analyzed. It was demonstrated that UV radiation inhibited the proliferation of cells apart from following exposure to low dose (1 J/cm2) UVA. Medium dose (5 J/cm2) UVA radiation had no adverse effects on lipid peroxidation and increased antioxidant levels in HaCaT cells. Medium (200 mJ/cm2) and high (400 mJ/cm2) doses of UVB radiation induced cellular damage due to increased lipid peroxidation as indicated by levels of malondialdehyde. Furthermore, A375 co-culture treatment induced a similar effect on the lipid peroxidation of HaCaT as with low dose UVB radiation. Therefore, the results of the present study determined that clinical doses of BB-UVA and NB-UVB radiation had varying effects on proliferation and related protein levels in HaCaT cells. Co-culture with A375 had similar effects as those of low dose UVA and UVB radiation, in which the PAR-2 expression was significantly upregulated.

UVA Irradiation Enhances Brusatol-Mediated Inhibition of Melanoma Growth by Downregulation of the Nrf2-Mediated Antioxidant Response.

Brusatol (BR) is a potent inhibitor of Nrf2, a transcription factor that is highly expressed in cancer tissues and confers chemoresistance. UVA-generated reactive oxygen species (ROS) can damage both normal and cancer cells and may be of potential use in phototherapy. In order to provide an alternative method to treat the aggressive melanoma, we sought to investigate whether low-dose UVA with BR is more effective in eliminating melanoma cells than the respective single treatments. We found that BR combined with UVA led to inhibition of A375 melanoma cell proliferation by cell cycle arrest in the G1 phase and triggers cell apoptosis. Furthermore, inhibition of Nrf2 expression attenuated colony formation and tumor development from A375 cells in heterotopic mouse models. In addition, cotreatment of UVA and BR partially suppressed Nrf2 and its downstream target genes such as HO-1 along with the PI3K/AKT pathway. We propose that cotreatment increased ROS-induced cell cycle arrest and cellular apoptosis and inhibits melanoma growth by regulating the AKT-Nrf2 pathway in A375 cells which offers a possible therapeutic intervention strategy for the treatment of human melanoma.

Control of the DNA-Binding and Antiproliferative Properties of Hydroxybenzo[b]quinolizinium Derivatives with pH and Light.

The interactions of 8-hydroxybenzo[b]quinolizinium and 9-hydroxybenzo[b]quinolizinium with DNA are investigated in detail. Specifically, spectrophotometric and spectrofluorimetric titrations, thermal DNA-denaturation experiments as well as CD- and LD-spectroscopic analysis show that a pH shift by just one or two orders of magnitude has a significant impact on the interactions of the acidic ligands with the nucleic acid. Both ligands bind with high affinity to DNA at pH 6 (Kb ≈105 m-1 ). At pH 7 or 8, however, the binding interactions are much weaker because of the formation of the corresponding charge-neutral conjugate bases, the affinity to DNA of which is reduced because of the resulting lack of a positive charge. Notably, the variation of DNA affinity occurs in a range that corresponds to the fluctuations of pH values under physiological conditions, so that these ligands may be employed to target DNA in tissue with particular pH values, especially, cancer cells. The antiproliferative activity of the title compounds under different conditions is also investigated. In the absence of irradiation, both compounds show only a modest cytotoxicity toward cancer cells. However, upon irradiation, even at low UV-A doses, a significant reduction of cell viability of tumor cell lines is induced by the ligands.