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UV Radiation Increases Carcinogenic Risks for Oral Tissues Compared to Skin
Abstract
People can expose their oral cavities to UV (290-400 nm) by simply opening their mouths while outdoors. They can also have their oral cavities exposed to UV indoors to different UV-emitting devices used for diagnoses, treatments and procedures like teeth whitening. Because the World Health Organization declared UV radiation as a complete human carcinogen in 2009, we asked if oral tissues are at a similar or higher carcinogenic risk compared to skin tissue. To understand the UVB (290-320 nm)-related carcinogenic risks to these tissues, we measured initial DNA damage in the form of cyclobutane pyrimidine dimers (CPD), the repair rate of CPD (24 h), and the number of apoptotic dead cells over time resulting from increasing doses of erythemally-weighted UV radiation. We used commercially available 3D-engineered models of human skin (EpiDerm(™) ), gingival (EpiGingival(™) ), and oral (EpiOral(™) ) tissues and developed an analytical approach for our tri-labeling fluorescent procedure to identify total DNA, CPD, and apoptotic cells so we can simultaneously quantify DNA repair rates and dead cells. Both DNA repair and apoptotic cell numbers are significantly lower in oral cells compared to skin cells. The combined results suggest UVB-exposed oral tissues are at a significantly higher carcinogenic risk than skin tissues. This article is protected by copyright. All rights reserved.
... According to a study conducted in the United States, ultraviolet radiation has the potential to increase the risk of cancer in not only the skin but in other tissues, as well, and has been associated with oral, pharyngeal, and cervical cancers, among others [2]. Although the World Health Organization has recognized UVR as a strong human carcinogen, there has not been a safe limit determined for the exposure of internal tissues to UVR [37]. Therefore, the present study evaluated the impact of UVB exposure at two doses (2.5 and 5 J/cm 2 ) on two types of oral carcinoma calls (tongue and pharyngeal), as well as on healthy gingival fibroblasts. ...
... Previous studies examined UVB's effects on a variety of cell lines, including myeloid leukemia, T-lymphoblastoid Molt-4, skin-derived primary fibroblasts, keratinocytes, and human tissues reconstructed from skin, gingiva, and oral tissues [37][38][39][40]. Moreover, UVB has been commonly used for diagnostic and treatment purposes in dental practices at a maximum intensity of 5 J/cm 2 [36]. ...
Ultraviolet radiation (UVR) is generally considered a primary tumorigenic agent. While UVR exposure has been studied, especially at the skin level, the impact of UV exposure on internal tissues and its effect on the appearance and the development of tumors has not yet been fully examined. Although there are maximum limits for UVR exposure on external tissues, other internal tissues, such as oral tissue, can be exposed to UVR as well. Over the course of diagnosis and treatment, oral cells may be exposed to ultraviolet radiation; however, there has not been an established limit for UV radiation exposure. Therefore, the aim of the current study was to examine the effects of ultraviolet-B (UVB) radiation at two doses (2.5 and 5 J/cm²) on tumor cells (pharyngeal carcinoma and tongue carcinoma) and healthy cells (gingival fibroblasts). The viability of the cells and their morphology, actin filaments, and nuclei structures; the expression of anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) genes; and the roles of caspases-3/7, 8, and 9 were determined after the cells had been exposed to UVB. The experiments revealed that both types of cell lines showed reductions in viability, especially at a dose of 5 J/cm². Additionally, apoptotic-like changes (rounding of the cells, the condensation of the nuclei, the re-organization of the actin filaments) were observed in all analyzed cells. The expression of anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) genes revealed that UVB (5 J/cm²) may induce apoptosis in both oral tumor and healthy cells. Moreover, an analysis of caspases-3/7, 8, and 9 showed that UVB exposure enhanced their activity, suggesting that cell death could be caused by both intrinsic and extrinsic apoptosis. Accordingly, UVB exposure at the maximum doses used in dental practices (5 J/cm²) induced nonselective apoptotic changes, thereby reducing both tumor and healthy cell viability.
... Because we found oral and gingival tissue cells to have significantly lower DNA damage repair and apoptotic cell death rates for UVB-induced damage, compared to skin tissue cells (39)(40)(41), we asked if the incidences of oral and pharyngeal cancer in the general U.S. population correlate with UV doses. To assess if such cancer in the general U.S. population correlates with average annual UV doses after planar correction (42), we analyzed IARC's epidemiology data for white and black males and females by weighting the population of each U.S. states' incidence and plotting by that state's population-centered latitude average annual personal UV dose estimates (43)(44)(45). ...
... Table I) but not for black females (Figure 3; Table II). Furthermore, we observed the incidence of oral and pharyngeal cancer combined in white males was over twice (10-15/100,000) that in white females (<5/100,000), possibly because males receive about 50% higher annual UV doses than females receive in the U.S. (40)(41)(42). Before Bonferroni correction but not after it, we also found a significant correlation between the increasing incidence of lip cancer and UV dose for white males (p=0.017) ...
Because we found UV-exposed oral tissue cells have reduced DNA repair and apoptotic cell death compared with skin tissue cells, we asked if a correlation existed between personal UV dose and the incidences of oral and pharyngeal cancer in the United States. We analyzed the International Agency for Research on Cancer's incidence data for oral and pharyngeal cancers by race (white and black) and sex using each state's average annual personal UV dose. We refer to our data as 'white' rather than 'Caucasian,' which is a specific subgroup of whites, and 'black' rather than African-American because blacks from other countries around the world reside in the U.S. Most oropharyngeal carcinomas harboured human papilloma virus (HPV), so we included cervical cancer as a control for direct UV activation. We found significant correlations between increasing UV dose and pharyngeal cancer in white males (p=0.000808) and females (p=0.0031) but not in blacks. Shockingly, we also found cervical cancer in whites to significantly correlate with increasing UV dose (p=0.0154). Thus, because pharyngeal and cervical cancer correlate significantly with increasing personal UV dose in only the white population, both direct (DNA damage) and indirect (soluble factors) effects may increase the risk of HPV-associated cancer.
... Specifically, we identified signatures consistent with pyrimidine dimer formation (SBS7a-c and DBS1) in oral HNC cases, indicative of DNA damage by UV light 12,23 . UV light has only been described as a risk factor for malignancies in the external lip 47 , but experimental evidence suggests that oral cavity epithelia are susceptible to this exposure, and its carcinogenic processes could be enhanced by tobacco smoking [48][49][50][51][52] . While we cannot exclude the possibility of other mutational processes eliciting CC>TT substitutions, such as those driven by reactive oxygen species 53 , the presence of ID13 signatures, identified in melanoma 12 , provides additional evidence supporting the role of sunlight exposure in oral HNC. ...
Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). We explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC samples from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and alcohol-related signatures, indicating a combined effect of these exposures. Tobacco smoking was associated with differences in the mutational spectra, repertoire of driver mutations in cancer genes and patterns of copy number change. Our results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.
... However, UV light has three types based on wavelength: UV-A (315-400 nm), UV-B (280-315 nm), and UV-C (100-280 nm), and while all types have antibacterial activity, UV-A only exhibits appreciable antimicrobial activity when utilizing relatively high uxes or long irradiation periods, compared to the higher energy UV-B and UV-C wavelengths, which have the disadvantage of having carcinogenic effects on human cells [7][8][9][10][11]. These factors severely limit the use of UV radiation as an intervention method to eradicate bacteria in the mouth. ...
Background
Despite the pivotal role of dental implants in restorative dentistry, persistent microbial adhesion and biofilm formation on implant surfaces pose significant challenges, often leading to peri-implant diseases and implant failure. Antimicrobial coatings, particularly those employing titanium dioxide (TiO2) and graphene, show promise in addressing these issues by harnessing their potent antimicrobial properties upon UV activation. Here, we present a facile method for depositing graphene onto TiO2-coated titanium substrates using a bulk turbostratic blasting technique and examine the potential synergistic antibacterial effect of graphene and TiO2 under UV-A irradiation.
Methods
Titanium and TiO2 substrates were coated with graphene using a bulk turbostratic technique and graphite powder. Deposition of graphene, TiO2, and graphene/TiO2 onto titanium substrates was assessed by Raman microscopy. Antibacterial activity was evaluated by colony-forming unit counts of Escherichia coli suspensions following exposure to varied durations of UV-A light in the presence of TiO2 and graphene/TiO2 substrates. To ensure reproducibility, three samples of each material underwent testing on three distinct days. Statistical comparison among study groups was conducted utilizing a two-tailed Student t-test, where values with P < 0.05 were considered statistically significant.
Results
Graphene deposition onto TiO2 was successfully accomplished using optimized turbostratic blasting parameters: 3 passes at 6.5 MPa pressure with substrates positioned 5 cm from the nozzle. Verification of successful deposition was confirmed by the presence of D, G, and 2D bands observed in the Raman spectra post-deposition. Importantly, few-layer graphene and not graphite was deposited under these conditions as evidenced by the position and width of the 2D band. Titanium substrates coated solely with TiO2 exhibited near-complete bacterial eradication upon 10 minutes of UV-A exposure. However, the introduction of a graphene layer led to a noticeable reduction in the antibacterial efficacy.
Conclusions
These results showcase the efficacy of a cost-effective turbostratic blasting method for graphene deposition onto TiO2 surfaces. While the impact of graphene on antimicrobial activity is evident, additional refinement of the TiO2/graphene interface is necessary to harness their synergistic effects. This optimization is pivotal for developing surface coatings that are amenable to processing by dental professionals and can robustly deter bacterial colonization on dental implants and abutments.
... The nucleotide excision repair pathway has been identified as a primary repair mechanism of DNA damage in mucosa 38 , which was observed to be lower in oral tissue compared to skin, and, therefore, could lead to the accumulation of DNA damage 39 . In a later study on 3D models, irradiated with UV-B, DNA repair and the amount of apoptotic cells were significantly lower in gingival and oral tissues compared to human skin 40 , which is in agreement with our findings. ...
The inactivation of multi resistant pathogens is an important clinical need. One approach is UV-C irradiation, which was previously not possible in vivo due to cytotoxicity. Recently, far UV-C irradiation at λ < 240 nm was successfully used on skin with negligible damage. A potential application site is the nasal vestibule, where MRSA accumulates and cannot be treated using antiseptics. We irradiated 3D mucosa models and excised human mucosa with 222 and 233 nm far UV-C in comparison to 254 nm and broadband UV-B. Eradication efficiency was evaluated by counting colony forming units; irritation potential was evaluated by hen’s egg-chorioallantoic membrane assay and trans epithelial electrical resistance; cell viability was assessed by MTT. DNA damage and cell protective mechanisms were evaluated immunohistopathologically. On mucosa models, MRSA reduced by ≈ 5 log10 for 60 mJ/cm² irradiation at 233 nm. A slightly increased cell viability was observed after 24 h. Lower doses showed lower irritation potential than the positive controls or commercial mouthwash, while 80 mJ/cm² had strong irritation potential. DNA damage occurred only superficially and decreased after 24 h. On excised human mucosa, < 10% of keratinocytes were affected after 150 mJ/cm² 222 nm or 60 mJ/cm² 233 nm.
... UVB-induced immunosuppression may facilitate oral microbial infection. Over-irradiation with UVB light can cause damage to oral tissues and increase the risk of oral cancer [95,96]. ...
Therapeutic light has been increasingly used in clinical dentistry for surgical ablation, disinfection, bio-stimulation, reduction in inflammation, and promotion of wound healing. Photodynamic therapy (PDT), a type of phototherapy, has been used to selectively destroy tumor cells. Antimicrobial PDT (a-PDT) is used to inactivate causative bacteria in infectious oral diseases, such as periodontitis. Several studies have reported that this minimally invasive technique has favorable therapeutic outcomes with a low probability of adverse effects. PDT is based on the photochemical reaction between light, a photosensitizer, and oxygen, which affects its efficacy. Low-power lasers have been predominantly used in phototherapy for periodontal treatments, while light-emitting diodes (LEDs) have received considerable attention as a novel light source in recent years. LEDs can emit broad wavelengths of light, from infrared to ultraviolet, and the lower directivity of LED light appears to be suitable for plaque control over large and complex surfaces. In addition, LED devices are small, lightweight, and less expensive than lasers. Although limited evidence exists on LED-based a-PDT for periodontitis, a-PDT using red or blue LED light could be effective in attenuating bacteria associated with periodontal diseases. LEDs have the potential to provide a new direction for light therapy in periodontics.
... In particular, UV radiation damages human lips, including photoaging, actinic cheilitis, and malignant tumor [4,5]. In comparison, oral exposure to UV radiation is associated with a higher risk of cancer than skin exposure [6]. ...
The vermilion of the human lip, covered by a skinny epithelium with little melanin, is quite susceptible to damage from ultraviolet (UV) radiation exposure. However, commercial sunscreen filters and indelible dyes used in lipsticks can cause health hazards after percutaneous absorption or accidentally oral administration. Inspired by plant pigmentation as natural filters to protect themselves against overexposure to UV, safer bio-based sunscreens of cellulose enveloped with anthocyanin (AN) were developed using bionic design. Cellulose nanocrystals (CNC), derived from acid hydrolysis of cellulose, reinforced enhancement of UV absorption and shielding properties of AN. This innovation addresses the issue that naturally sourced UV filter application to sunscreen does not achieve a desired sun protection factor (SPF) value because of the low specific extinction value (E1,1). We also stated that the diverse formula of anthocyanin sunscreen lipsticks with CNC exhibited 10 times more SPF value than AN alone. Furthermore, they possess competitive benefits such as pleasing texture, superior adhesion, impermeable, nonphototoxicity, ease of application, and removal. This work provides a promising proof-of-concept for studying the features of natural sunscreens in the design of simple, safe, efficient, and green sunscreens.
... Several studies have demonstrated that the risk of cancer is increased by several other factors such as immune conditions (e.g., congenital defects in the immune system and organ transplant recipients who are administered immunosuppressant drugs), environmental pollutants (e.g., arsenic, chromium and nickel), occupational exposures (e.g., ultraviolet radiation), microorganisms (e.g., bacteria), and genetic diseases (e.g., Fanconi anemia, dyskeratosis congenita, and Bloom syndrome) [61][62][63][64]. ...
The etiological factors of oral cancer are complex including drinking alcohol, smoking tobacco, betel quid chewing, human papillomavirus infection, and nutritional deficiencies. Understanding the molecular mechanism of oral cancer is vital. The traditional treatment for patients with oral squamous cell carcinoma (e.g., surgery, radiotherapy, and chemotherapy) and targeted molecular therapy still have numerous shortcomings. In recent years, the use of phytochemical factors to prevent or treat cancer has received increasing attention. These phytochemicals have little or no toxicity against healthy tissues and are thus ideal chemopreventive agents. However, phytochemicals usually have low water solubility, low bioavailability, and insufficient targeting which limit therapeutic use. Numerous studies have investigated the development of phytochemical delivery systems to address these problems. The present article provides an overview of oral cancer including the etiological factors, diagnosis, and traditional therapy. Furthermore, the classification, dietary sources, anticancer bioactivity, delivery system improvements, and molecular mechanisms against oral cancer of phytochemicals are also discussed in this review.
... In contrast to skin, human oral mucosa has no keratinized squamous epithelium, which makes it potentially more sensitive to damage from CAP treatment. It is known that oral tissue is more susceptible to carcinogenic changes due to UV radiation than the skin [26,27]. Up to now, only one very small in-vivo pilot study with six rabbits has examined the oral mucosa response after plasma treatment [28]; on days one and five after treatment no severe mucous membrane irritation could be shown. ...
Cold atmospheric pressure plasma (CAP) has been investigated with promising results for peri-implant diseases treatment. However, prior to in-vivo applications of CAP sources in humans, short-term harmful mucosal damage or other unwanted side effects have to be reviewed. 180 male mice (B6C3F1) were divided into twelve treatment groups (n = 15). The right buccal cheek mucosa was treated with CAP. The first and second group each received continuous 10 sec irradiation with 2 different plasma sources (kINPen09, PS-MWM). The third group was treated with the kINPen09 for one minute. Control groups were treated with a corresponding dose of ultraviolet light for 8 seconds or 48 seconds and the other one was left untreated. The animals were weighed before and after treatment. The animals were sacrificed one day or one week after exposure. Stained tissue samples were histologically examined for tissue damage independently by two experienced pathologists. One day after CAP treatment histological analysis showed focal mucosal erosion with superficial ulceration and necrosis accompanied by a mild inflammatory reaction. One week after CAP treatment, the mucosal defects were completely re-epithelialized, associated with remnants of granulation tissue in the stroma irrespective of treatment duration. Furthermore, no cytological atypia was found and no severe weight loss occurred. The control groups did not show any alterations at all. CAP treatment led to a superficial mucosal damage that healed within few days. Nonetheless, further long-term experiments are necessary to exclude undesirable side effects after longer observation time. Particularly, potential carcinogenic effects must be ruled out prior to the application of CAP treatment in daily dental practice.
... The EpiGingival ™ (MatTek) model was also used, which consists of normal human oral keratinocytes that are differentiated into tissues with a cornified, gingival phenotype that is considered to be an appropriate representation of lip skin. [49][50][51][52] The tissue models were topically treated with distilled water (control), the test lip cream formulation without UV filters (placebo), or the test lip cream formulation with UV filters. One hour after topical treatment, the tissues were exposed to either UVA (30, 50, or 70 J/cm 2 ) or UVB (150 mJ/cm 2 ) radiation. ...
Purpose
These studies describe the testing of a novel, daily-use lip cream designed for individuals with lips prone to recurrent herpes labialis (RHL) that protects against environmental triggers.
Subjects and methods
In vitro occlusive and in vitro and in vivo photoprotection analyses, a characterization of normal vs dry lips, and a randomized, evaluator-blinded, clinical trial that assessed the lip cream in healthy subjects with dry lips were conducted. In the clinical trial, subjects applied the lip cream or were untreated and evaluated using transepidermal water loss (TEWL), corneometry, visual assessments of lip dryness, expert photographic evaluations, and subject-rated outcomes.
Results
The lip cream’s in vitro water vapor transmission rate (84.1 g/(m² h)) indicated moderate occlusivity. The lip cream, but not placebo or control (water), reduced ultraviolet A (UVA)- and UVB-induced DNA damage, and tumor necrosis factor-α (EpiDermFT) and pros-taglandin E2 release (EpiDermFT and EpiGingival™). The lip cream’s in vivo sun protection factor (SPF) was 12.2 (lower confidence limit, 11.3) and SPF/UVA protection factor ratio was 0.9. The characterization of dry vs normal lips identified differences in moisturization. In the clinical trial, the lip cream significantly decreased TEWL (difference: −7.19 [95% CI: −11.41, −2.98]; P<0.01), increased corneometry (difference: 4.62 [95% CI: 1.05, 8.19]; P<0.05), and reduced visual dryness (difference: −1.48 [95% CI: 2.24, −0.71]; P<0.001) compared to untreated subjects. Significant benefits were also observed on expert photographic assessments of scaling (difference: −0.89 [95% CI: −1.75, −0.03]; P< 0.05), cupping (difference: −1.50 [95% CI: −2.30, −0.70]; P<0.001), and healthy appearance (difference: −1.44 [95% CI: −2.29, −0.58]; P<0.01); differences in overall healthy appearance were not significant (P=0.51). Subject-rated assessments indicated improvements in cracking, dryness, and flaking in the lip cream group but worsening in untreated subjects.
Conclusion
These studies indicate that this novel, daily-use lip cream protects against UV radiation, drying, and chapping, which are established environmental RHL triggers.
... In the context of oral health, we recently reported that buccal and gingival epithelia-derived organotypic models recapitulated the pathophysiological conditions and molecular changes observed in the oral tissues of smokers (Zanetti et al., 2016(Zanetti et al., , 2017Schlage et al., 2014). Several other studies also support these findings (Agrawal et al., 2013;Mitchell et al., 2012;Yang et al., 2011). Furthermore, in accord with the "field of injury" concept (Steiling et al., 2008), we identified shared responses of buccal, nasal, and bronchial organotypic epithelial cultures to CS (Iskandar et al., 2017c). ...
Cigarette smoke (CS) is affecting considerably the oral mucosa. Heating, instead of burning, tobacco reduces consistently the amount of toxic compounds and may exert a lower impact on oral health than combusted cigarettes. The carbon-heated tobacco product 1.2 (CHTP1.2) is a potential modified risk tobacco product (MRTP) based on heat-not-burn technology. Using a systems toxicology assessment framework, we compared the effects of exposure to CHTP1.2 aerosol with those of CS from a reference cigarette (3R4F). Human organotypic cultures derived from buccal and gingival epithelia were exposed acutely (28-min) or repeatedly (28 min/day for 3 days), respectively, to two matching concentrations of CHTP1.2 aerosol or 3R4F CS, and a non-diluted (100%) CHTP1.2 aerosol. The results showed an absence of cytotoxicity, reduction in pathophysiological alterations, toxicological marker proteins, and inflammatory mediators following exposure to CHTP1.2 aerosol compared with 3R4F CS. Changes in mRNA and miRNA expression were linked by an integrative analysis approach, suggesting a regulatory role of miRNAs in several smoke/disease-relevant biological processes induced by 3R4F CS. The identification of mechanisms by which potential MRTPs can reduce the impact of tobacco use on biological systems is of great importance in understanding the molecular basis of the smoking harm reduction paradigm.
... MatTek, Ashland, MA, USA) (Hai et al., 2006). Several aspects of the in vivo situation are recapitulated by these gingival cultures: EpiGingival™ cultures resemble the in vivo paradigm under cytomegalovirus infection (Hai et al., 2006), they show good reproducibility of the human situation for carcinogenic studies (Agrawal et al., 2013;Mitchell et al., 2012), and they are suitable for oral care product testing (Yang et al., 2011). In a recent study, we found that gingival cultures also recapitulate several effects of in vivo CS exposure, including the release of inflammatory mediators and activation of cell stress networks . ...
... MatTek, Ashland, MA, USA) (Hai et al., 2006). Several aspects of the in vivo situation are recapitulated by these gingival cultures: EpiGingival™ cultures resemble the in vivo paradigm under cytomegalovirus infection (Hai et al., 2006), they show good reproducibility of the human situation for carcinogenic studies (Agrawal et al., 2013;Mitchell et al., 2012), and they are suitable for oral care product testing (Yang et al., 2011). In a recent study, we found that gingival cultures also recapitulate several effects of in vivo CS exposure, including the release of inflammatory mediators and activation of cell stress networks . ...
Smoking is one of the major lifestyle-related risk factors for periodontal diseases. Modified risk tobacco products (MRTP) offer a promising alternative in the harm reduction strategy for adult smokers unable to quit. Using a systems toxicology approach, we investigated and compared the exposure effects of a reference cigarette (3R4F) and a heat-not-burn technology-based candidate MRTP, the Tobacco Heating System (THS) 2.2. Human gingival epithelial organotypic cultures were repeatedly exposed (3 days) for 28 min at two matching concentrations of cigarette smoke (CS) or THS2.2 aerosol. Results showed only minor histopathological alterations and minimal cytotoxicity upon THS2.2 aerosol exposure compared to CS (1% for THS2.2 aerosol vs. 30% for CS, at the high concentration). Among the 14 proinflammatory mediators analyzed, only 5 exhibited significant alterations with THS2.2 exposure compared with 11 upon CS exposure. Transcriptomic and metabolomic analysis indicated a general reduction of the impact in THS2.2 aerosol-exposed samples with respect to CS (∼79% lower biological impact for the high THS2.2 aerosol concentration compared to CS, and 13 metabolites significantly perturbed for THS2.2 vs. 181 for CS). This study indicates that exposure to THS2.2 aerosol had a lower impact on the pathophysiology of human gingival organotypic cultures than CS.
... 15 Agrawal et al showed UV radiation used in procedures like teeth whitening increases carcinogenic risks for oral tissues compared to the skin. 16 David et al assessed the molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation. They showed that human nasal mucosa was capable of efficient repair of UV-induced DNA damage and suggest that UV phototherapy can be used in the treatment of AR. 17 About the carcinogenic effect of phototherapy, we confronted contradictory conclusions in different studies. ...
Allergic rhinitis is one of the most common health problems with a major effect on the quality of life. We intended to treat Allergic Rhinitis (AR) in patients who are either unresponsive to antihistamines or their job requires optimal alertness that may be disturbed by antihistamine's side effects and those who do not comply with the regular use. We tried short term phototherapy and evaluated its effect on AR. As phototherapy is effective in the treatment of atopic dermatitis (AD) and the same allergens can produce both AD and AR, phototherapy is proposed as a new tool in the AR treatment. In AD, phototherapy causes induction of apoptosis in infiltrating T cells and other immunomodulatory effects. We performed a randomized single-blind study to investigate the effect of low-dose phototherapy in AR patients. Among AR patients who did not respond to local and systemic therapy, we chose 62 allergic patients all above 25 years of age with moderate to severe AR whose disease was verified by allergy skin test or specific IgE to allergens; then, they were randomly divided into 31 patients as treatment group and 31 patients as control group. In treatment groups, we used a mixture of UVA, UVB and visible light. In the control group, we used visible light alone as placebo. Then we evaluated the level of response to treatment in two groups and compared them according to Total Nasal Symptom scores (TNSS) and Global Severity Scores (GSS) and Rhinoconjunctivitis Quality of Life Questionnaires (RQLQ) symptom scores. We found out that phototherapy in the treatment group in comparison with placebo was effective in treatment of AR (p-value <0.001). However, we recommend that for substantiation of the claim, further investigations are still required. © Summer 2016, Iran J Allergy Asthma Immunol. All rights reserved.
... The main theory behind cancer formation is that toxic substances, heavy metals, radiation (Davis et al., 2013), ultraviolet rays (Agrawal et al., 2013) and other physical and chemical stimuli cause genetic mutations, turning normal cells into cancer cells (Benigni and Bossa, 2011). Furthermore, with certain family genetic characteristics or genetic deficiencies, there is a higher possibility for normal cells to become cancer cells. ...
... 29 UV-B radiation was also excluded from the investigation, based on recent findings indicating enhanced sensitivity of oral tissues to UV-B. 30 The UV-A band was included, as it is supposedly less carcinogenic than UV-B because of its lesser photon energy, and yet exhibiting considerable photochemical effects. 31,32 The VIS violet light was selected because of a demonstrated bactericidal effect on a wide range of medically important bacteria, and increased human safety because of its lower photon energy. ...
Objective:
The aim of this study was to quantitatively investigate the efficiency of the ultraviolet (UV) and visible light in eradication of Candida albicans in vitro; in particular, to determine, for selected wavelengths, the specific eradication coefficients and thresholds in terms of energy density levels required to effect 3.0log10 and 4.0log10 reduction.
Background data:
Oral candidosis is the most common infection of the oral cavity and is caused by Candida species. The widespread use of topical and systemic antifungal agents as conventional treatment for oral candidosis has resulted in the development of resistance in C. albicans. Therefore, it has become necessary to develop alternative therapies for the treatment of oral candidosis.
Methods:
C. albicans ATCC(®) 90028(™) was irradiated with 254 nm, 365 nm, 406 nm, 420 nm, and broadband Xe spectrum. For each wavelength, a fit of experimental data (survival fraction vs. applied energy density) with an exponential decay function enabled estimation of the specific eradication coefficients and thresholds.
Results:
Based on estimated specific efficiencies (Δ) and eradication thresholds (ET) of the investigated wavelengths, the ranking in eradication efficiency of C. albicans (most to least effective) is: 254 nm (Δ=6.1 mJ/cm(-2), ET99.99=56 mJ/cm(-2)), broadband Xe spectrum (Δ=27.7 mJ/cm(-2), ET99.99=255 mJ/cm(-2)), 365 nm (Δ=4.3 J/cm(-2), ET99.99=39 J/cm(-2)), 420 nm (Δ=0.65 J/cm(-2), ET99.99=6 J/cm(-2)), and 406 nm (Δ=11.4 J/cm(-2), ET99.99=104 J/cm(-2)).
Conclusions:
The results provide insight into the wavelength-dependent dynamics of eradication of C. albicans. For each investigated wavelength, the eradication coefficient and corresponding eradication threshold were estimated. The observed different eradication efficiencies are consequence of different spectrally dependent inactivation mechanisms. The established methodology enables unambiguous quantitative comparison of eradication efficiencies of optical radiation and selection of most effective wavelengths for clinical and therapeutic use.
The increasing needs for protection from COVID-19 pandemic and biological-related risks together with the broader availability of new technologies have led to a widespread use of UV germicidal lamps in many contexts. Safety is a major concern in the use of these devices especially in emergency situations. Skin and eye are commonly recognized as target organs for exposure to ultraviolet radiation (UVR). Nevertheless, adverse effects were also observed in the oral cavity of two healthcare workers after an accidental exposure to a germicidal lamp in hospital pharmacy. An experimental on-the-field study was set up to provide a risk assessment of accidental UVR exposure in the oral cavity. An adult manikin was adapted to reproduce real exposure in different postures. The oral cavity was exposed for 30 min (half of the time the workers spent at the workstation). The accumulated radiant energy per unit area was slightly above the limit for human biologically effective radiant exposure to UVR of eyes and skin within an 8-h period according to the ICNIRP guideline (30 J/m2). A UV-C exposure > 100 J/m2 was assessed in correspondence to the lips of the manikin. The high humidity presents in the oral cavity and the absence of the stratum corneum in some areas might enhance the epithelium photo-damage due to UV-C, highlighting a potential risk of adverse effects to the oral cavity from exposure to artificial sources of UV-C radiation. Specific UVR exposure limits for the oral mucosa could be developed to prevent and protect workers’ health.
Since the oral cavity comes into contact with several xenobiotics (dental materials, oral hygiene formulations, drugs, or tobacco products), it is one major site for toxicity manifestation. Multiple parameters are assessed during toxicity testing (cell viability and proliferation, apoptosis, morphological changes, genotoxicity, oxidative stress, and inflammatory response). Due to the complexity of the oral cavity environment, researchers have made great efforts to design better in vitro models that mimic natural human anatomic and functional features. The present review describes the in vitro methods currently used to investigate the toxic potential of various agents on oral cavity tissues and their evolution from simple 2D cell culture systems to complex organ-a-chip designs.
Tissue-engineered oral epithelium (ΤΕΟΕ) was developed after comparing various culture conditions, including submerged (SUB) and air-liquid interface (ALI) human cell expansion options. Barrier formation was evaluated via transepithelial electrical resistance (TEER) and calcein permeation via spectrofluorometry. TEOE was further assessed for long-term viability via live/dead staining and development of intercellular connections via transmission electron microscopy. Tissue architecture was evaluated via histochemistry and the expression of pancytokeratin (pCK) via immunohistochemistry. The effect of two commonly used dental resinous monomers on TEOE was evaluated for alterations in cell viability and barrier permeability. ALI/keratinocyte growth factor-supplemented (ALI-KGS) culture conditions led to the formation of an 8-20-layer thick, intercellularly connected epithelial barrier. TEER values of ALI-KGS-developed TEOE decreased compared with all other tested conditions, and the established epithelium intensively expressed pCK. Exposure to dental monomers affected the integrity and architecture of TEOE and induced cellular vacuolation, implicating hydropic degeneration. Despite structural modifications, the permeability of TEOE was not substantially affected after exposure to the monomers. In conclusion, the biological properties of the TEOE mimicking the physiological functional conditions and its value as biocompatibility assessment tool for dental materials were characterized.
Oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) represent a significant global health burden due to their potential for malignant transformation and the challenges associated with their diagnosis and treatment. Chemoprevention, an innovative approach aimed at halting or reversing the neoplastic process before full malignancy, has emerged as a promising avenue for mitigating the impact of OPMD and OSCC. The pivotal role of chemopreventive strategies is underscored by the need for effective interventions that go beyond traditional therapies. In this regard, chemopreventive agents offer a unique opportunity to intercept disease progression by targeting the molecular pathways implicated in carcinogenesis. Natural compounds, such as curcumin, green tea polyphenols, and resveratrol, exhibit anti-inflammatory, antioxidant, and anti-cancer properties that could make them potential candidates for curtailing the transformation of OPMD to OSCC. Moreover, targeted therapies directed at specific molecular alterations hold promise in disrupting the signaling cascades driving OSCC growth. Immunomodulatory agents, like immune checkpoint inhibitors, are gaining attention for their potential to harness the body’s immune response against early malignancies, thus impeding OSCC advancement. Additionally, nutritional interventions and topical formulations of chemopreventive agents offer localized strategies for preventing carcinogenesis in the oral cavity. The challenge lies in optimizing these strategies for efficacy, safety, and patient compliance. This review presents an up to date on the dynamic interplay between molecular insights, clinical interventions, and the broader goal of reducing the burden of oral malignancies. As research progresses, the synergy between early diagnosis, non-invasive biomarker identification, and chemopreventive therapy is poised to reshape the landscape of OPMD and OSCC management, offering a glimpse of a future where these diseases are no longer insurmountable challenges but rather preventable and manageable conditions.
The high incidence of oral cancer combined with excessive treatment cost underscores the need for novel oral cancer preventive and therapeutic options. The value of natural agents, including plant secondary metabolites (phytochemicals), in preventing carcinogenesis and representing expansive source of anticancer drugs have been established. While fragmentary research data are available on antioral cancer effects of phytochemicals, a comprehensive and critical evaluation of the potential of these agents for the prevention and intervention of human oral malignancies has not been conducted according to our knowledge. This study presents a complete and critical analysis of current preclinical and clinical results on the prevention and treatment of oral cancer using phytochemicals. Our in‐depth analysis highlights anticancer effects of various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur‐containing compounds, against numerous oral cancer cells and/or in vivo oral cancer models by antiproliferative, proapoptotic, cell cycle‐regulatory, antiinvasive, antiangiogenic, and antimetastatic effects. Bioactive phytochemicals exert their antineoplastic effects by modulating various signaling pathways, specifically involving the epidermal growth factor receptor, cytokine receptors, toll‐like receptors, and tumor necrosis factor receptor and consequently alter the expression of downstream genes and proteins. Interestingly, phytochemicals demonstrate encouraging effects in clinical trials, such as reduction of oral lesion size, cell growth, pain score, and development of new lesions. While most phytochemicals displayed minimal toxicity, concerns with bioavailability may limit their clinical application. Future directions for research include more in‐depth mechanistic in vivo studies, administration of phytochemicals using novel formulations, investigation of phytocompounds as adjuvants to conventional treatment, and randomized clinical trials.
The oral mucosa can become irritated by oral care products and lip cosmetics. Therefore, it is important to determine the irritation potential of their ingredients and products during safety evaluations. We developed a method for oral mucosal irritation test using EpiOral, which is a three-dimensional cultured model. Exposure of sodium lauryl sulphate (SLS) to EpiOral showed a dose-dependent decrease in cell viability. Under 120 min exposure conditions, SLS irritation was detected when 60% cell viability was set as a criterion. Evaluation of the irritancy of SLS and four other raw materials used in oral products at three laboratories under the above conditions confirmed good transferability of the test. Focused on the similarity of the oral and eye mucous, 32 chemicals categorised by the UN-GHS eye-irritation classification were evaluated to ensure the reliability of our criteria at these laboratories. The concordance rate between the UN-GHS classification and our test results was 100% for irritants and 60% for non-irritants. The good intra-laboratory reproducibility of our test was confirmed from the evaluation results of negative and positive controls, and the good inter-laboratory reproducibility was confirmed from the results of 32 chemicals. These findings showed that oral mucosal irritation can be evaluated using EpiOral.
Lifestyle factors are known to be influential determinants of health. According to the World Health Organization (WHO), approximately one third of deaths involve unhealthy lifestyle habits. Among lifestyle risk factors for head and neck cancers (HNC), alcohol consumption and smoking have an undeniable role in the multifactorial aetiology of the disease. In recent years, the promotion of healthy lifestyle choices has gained significant attention as contributory to improving health and disease prevention. Interventions to tackle these risk factors are vitally important in disease prevention and progression. However, in order to effectively prevent the disease and reduce the risk factors, it is crucial to identify what upstream reasons lead to the adoption of these lifestyle risk factors in the first place. Stress being a constant aspect of modern-day life is known to contribute to alcohol and smoking practices. In this review paper, relevant literature was searched in PubMed database for stress, lifestyle factors, HNC and cancer to explore the role of stress and its associated biological pathways as an upstream factor in the adoption of lifestyle risk factors that cause HNC. It highlights the importance of stress pathways and the Hypothalamus Pituitary Adrenal (HPA) axis as a locus of interaction between stress, alcohol, smoking and cancer. Despite their widely accepted harmful effects, alcohol and smoking remain deeply rooted in contemporary life. A greater understanding of the impact of stress on lifestyle choices and an exploration of the mechanisms resulting in stress, alcohol- and smoking- related cancer may highlight opportunities for improved prevention measures through the modification of unhealthy lifestyle choices.
Solar ultraviolet radiation (UV) can cause DNA damage in microorganisms. Flap endonuclease 1 (FEN1) is a structure-specific nuclease and plays important roles in DNA replication and repair. At present, the properties and functions of FEN1 have not been characterized in detail in invertebrates such as Bombyx mori. In this study, Bombyx mori FEN1 (BmFEN1) was expressed in E. coli, and was shown to have nuclease activity that nonspecifically cleaved DNA in vitro. However, inside the cell, BmFEN1 did not cleave DNA randomly. Truncated BmFEN1 missing the nuclear localization signal (346-380 aa) still had the nuclease activity, but was no longer precisely localized to the sites of UV-induced DNA damage. It was further found that BmFEN1 favored the faster repair of UV-damaged DNA. The present study will provide a reference for further understanding the functions of BmFEN1 and UV-induced DNA damage repair mechanisms in insects.
Oral lichen planus (OLP) is a chronic inflammatory disorder with multifactorial etiopathogenesis. Immune dysregulation plays a critical role in the development and progression of this disease. Patients’ life may be affected by pain caused by atrophic-erosive lesions. Treatment is usually symptomatic given the obscure etiology. Topical steroids remain the mainstay of management. However, their therapeutic benefits are not always evident. There are substantial data on the possible therapeutic strategies that are effective in OLP cases refractory to steroids. This review provides an overview of the current approaches for the management of steroid-refractory OLP. The miscellaneous treatment regimens include tacrolimus, pimecrolimus, thalidomide, low-level laser therapy, photodynamic therapy, and surgical excision. Some results obtained from these studies were promising. However, further studies, especially randomized controlled trials with strict inclusion and exclusion criteria and larger sample sizes, are required for the evaluation of long-term safety and efficacy of these therapies.
An immunoassay based on CE–LIF was developed for the simultaneous detection of cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts (6-4PPs) in genomic DNA irradiated with UVB or natural sunlight. Human cells were first exposed to varying amounts of UVB or natural sunlight to induce DNA damage. Genomic DNA was extracted and incubated with anti-CPD and anti-6-4PP primary antibodies attached to secondary antibodies with a fluorescent quantum dot (QD) reporter that emitted either red or yellow fluorescence. CE was used to separate the unbound antibodies from those bound to the photoproducts, and LIF with appropriate optical filters was used to separate the fluorescence signals from each QD to individual photomultiplier tubes for simultaneous photoproduct detection. Using this strategy, photoproducts were detected from ∼6 ng (200 ng μL−1) of DNA under a low UVB fluence of 65 J m−2 for CPDs or 195 J m−2 for 6-4PPs. This assay was also the first to demonstrate the detection of CPDs in human cells after only 15 min of irradiation under natural sunlight.
This study investigated the molecular mechanisms of polypeptides from Chlamys farreri (PCF)'s anti-apoptotic effects in ultraviolet A-rays (UVA) exposed HaCaT cells. UVA-induced apoptosis in HaCaT cells was confirmed with Hoechst 33258 fluorescent staining; PCF treatment inhibited UVA-induced apoptosis in HaCaT cells, increased transcriptional activities of heat shock factor protein 1 (HSF1) and the expression of heat shock protein 70 (HSP70), whereas inhibited activation of c-Jun N-terminal kinases (JNK), expression of xanthine oxidese (XO), inducible nitric oxide synthase (iNOS) and release of nitric oxide (NO)/reactive oxygen species (ROS). Meanwhile, the HSF1 transcription inhibitor quercetin increased UVA-induced apoptosis, activation of JNK, expression of XO and iNOS and release of NO/ROS. Among the two NO release peaks we found in UVA exposed HaCaT cells, XO inhibitor oxypurinol was found to be able to inhibit NO release at 3h post UVA exposure but not 18h, while iNOS inhibitor S-methylisothiourea sulfate (SMT) was found to inhibit iNOS expression and NO release at 18h but not 3h. PCF's protection against UVA-induced apoptosis in HaCaT cells involves increased transcriptional activity of HSF1, increased expression of HSP70, and the subsequential inhibition of JNK pathway, XO and iNOS expression and ROS/NO release.
Objective
We used reflectance and fluorescence spectroscopy to noninvasively and quantitatively distinguish benign from dysplastic/malignant oral lesions. We designed diagnostic algorithms to account for differences in the spectral properties among anatomic sites (gingiva, buccal mucosa, etc).
Methods
In vivo reflectance and fluorescence spectra were collected from 71 patients with oral lesions. The tissue was then biopsied and the specimen evaluated by histopathology. Quantitative parameters related to tissue morphology and biochemistry were extracted from the spectra. Diagnostic algorithms specific for combinations of sites with similar spectral properties were developed.
Results
Discrimination of benign from dysplastic/malignant lesions was most successful when algorithms were designed for individual sites (area under the receiver operator characteristic curve [ROC-AUC], 0.75 for the lateral surface of the tongue) and was least accurate when all sites were combined (ROC-AUC, 0.60). The combination of sites with similar spectral properties (floor of mouth and lateral surface of the tongue) yielded an ROC-AUC of 0.71.
Conclusions
Accurate spectroscopic detection of oral disease must account for spectral variations among anatomic sites. Anatomy-based algorithms for single sites or combinations of sites demonstrated good diagnostic performance in distinguishing benign lesions from dysplastic/malignant lesions and consistently performed better than algorithms developed for all sites combined.
Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking.
HPV status was determined for all 271 oropharyngeal cancers (1984-2004) collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses.
HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay (P trend < .05). For example, HPV prevalence by Inno-LiPA increased from 16.3% during 1984 to 1989 to 71.7% during 2000 to 2004. Median survival was significantly longer for HPV-positive than for HPV-negative patients (131 v 20 months; log-rank P < .001; adjusted hazard ratio, 0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar periods for HPV-positive (P = .003) but not for HPV-negative patients (P = .18). Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per 100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to 53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020.
Increases in the population-level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection.
Objectives
We used reflectance and fluorescence spectroscopy to noninvasively and quantitatively distinguish benign from dysplastic/malignant oral lesions. We designed diagnostic algorithms to account for differences in the spectral properties among anatomic sites (gingiva, buccal mucosa, etc).
Methods
In vivo reflectance and fluorescence spectra were collected from 71 patients with oral lesions. The tissue was then biopsied and the specimen evaluated by histopathology. Quantitative parameters related to tissue morphology and biochemistry were extracted from the spectra. Diagnostic algorithms specific for combinations of sites with similar spectral properties were developed.
Results
Discrimination of benign from dysplastic/malignant lesions was most successful when algorithms were designed for individual sites (area under the receiver operator characteristic curve [ROC-AUC], 0.75 for the lateral surface of the tongue) and was least accurate when all sites were combined (ROC-AUC, 0.60). The combination of sites with similar spectral properties (floor of mouth and lateral surface of the tongue) yielded an ROC-AUC of 0.71.
Conclusions
Accurate spectroscopic detection of oral disease must account for spectral variations among anatomic sites. Anatomy-based algorithms for single sites or combinations of sites demonstrated good diagnostic performance in distinguishing benign lesions from dysplastic/malignant lesions and consistently performed better than algorithms developed for all sites combined.
In order to evaluate the impact of anatomy on the spectral properties of oral tissue, we used reflectance and fluorescence spectroscopy to characterize nine different anatomic sites. All spectra were collected in vivo from healthy oral mucosa. We analyzed 710 spectra collected from the oral cavity of 79 healthy volunteers. From the spectra, we extracted spectral parameters related to the morphological and biochemical properties of the tissue. The parameter distributions for the nine sites were compared, and we also related the parameters to the physical properties of the tissue site. k-Means cluster analysis was performed to identify sites or groups of sites that showed similar or distinct spectral properties. For the majority of the spectral parameters, certain sites or groups of sites exhibited distinct parameter distributions. Sites that are normally keratinized, most notably the hard palate and gingiva, were distinct from nonkeratinized sites for a number of parameters and frequently clustered together. The considerable degree of spectral contrast (differences in the spectral properties) between anatomic sites was also demonstrated by successfully discriminating between several pairs of sites using only two spectral parameters. We tested whether the 95% confidence interval for the distribution for each parameter, extracted from a subset of the tissue data could correctly characterize a second set of validation data. Excellent classification accuracy was demonstrated. Our results reveal that intrinsic differences in the anatomy of the oral cavity produce significant spectral contrasts between various sites, as reflected in the extracted spectral parameters. This work provides an important foundation for guiding the development of spectroscopic-based diagnostic algorithms for oral cancer.
The use of UVB and/or UVA emitting devices for cosmetic tanning is widespread in Western populations including young people and is especially prevalent in females. Several epidemiological studies, although not all, have shown a significant relationship between the use of tanning devices and malignant melanoma after, in some cases, adjustment for confounding factors such as solar ultraviolet radiation (UVR) exposure. A relationship between solar exposure, especially intermittent exposure, and malignant melanoma is well established so it is not surprising that a similar connection has been reported for the use of tanning devices. Several epidemiological studies show that childhood exposure to sunlight is a risk factor for malignant melanoma and this may also be the case for the use of tanning devices, especially if sunburns are obtained. Some studies have evaluated the relationship between the use of tanning devices and non-melanoma skin cancer and at least one has suggested an association. The use of tanning devices by a substantial minority of young people is a worrying trend in terms of a likely increased incidence of malignant melanoma, and possibly non-melanoma cancers in the future. Although two recent reviews by epidemiologists conclude that a clear link between tanning devices and malignant melanoma is yet to be proven, there is a strong case for effective legislation to prohibit the use of tanning devices by people under 18 yr of age.
Apoptotic elimination of UV-damaged cells from the epidermis is an important step in preventing both the emergence and expansion of cells with carcinogenic potential. A pivotal event in apoptosis is the release of apoptogenic factors from the mitochondria, although the mechanisms by which the different proteins are released are not fully understood. Here we demonstrate that UV radiation induced the mitochondrial to nuclear translocation of apoptosis inducing factor (AIF) in normal skin. The human papillomavirus (HPV) E6 protein prevented release of AIF and other apoptotic factors such as cytochrome c and Omi from mitochondria of UV-damaged primary epidermal keratinocytes and preserved mitochondrial integrity. shRNA silencing of Bak, a target for E6-mediated proteolysis, demonstrated the requirement of Bak for UV-induced AIF release and mitochondrial fragmentation. Furthermore, screening non-melanoma skin cancer biopsies revealed an inverse correlation between HPV status and AIF nuclear translocation. Our results indicate that the E6 activity towards Bak is a key factor that promotes survival of HPV-infected cells that facilitates tumor development.
People can get oral cancers from UV (290-400 nm) exposures. Besides high outdoor UV exposures, high indoor UV exposures to oral tissues can occur when consumers use UV-emitting tanning devices to either tan or whiten their teeth. We compared the carcinogenic risks of skin to oral tissue cells after UVB (290-320 nm) exposures using commercially available 3D-engineered models for human skin (EpiDerm(™) ), gingival (EpiGing(™) ), and oral (EpiOral(™) ) tissues. To compare the relative carcinogenic risks, we investigated the release of cytokines, initial DNA damage in the form of cyclobutane pyrimidine dimers (CPDs), repair of CPDs and apoptotic cell numbers. We measured cytokine release using cytometric beads with flow cytometry and previously developed a fluorescent immunohistochemical assay to quantify simultaneously CPD repair rates and apoptotic cell numbers. We found interleukin-8 (IL-8) release and the initial CPDs are significantly higher, while the CPD repair rates and apoptotic cell numbers are significantly lower for oral compared to skin tissue cells. Thus, the increased release of the inflammatory cytokine IL-8 along with inefficient CPD repair and decreased death rates for oral compared to skin tissue cells suggests mutations are accumulating in the surviving population of oral cells increasing people's risks for getting oral cancers. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.
There is a continuously growing interest in medical applications of ultraviolet radiation (UV-A and long-wavelength UV-B) especially for laser surgery, phototherapy and photodiagnostics of human internal organs. UV-B and UV-A radiation is potentially mutagenic, however, there has been very little information published to date concerning the significance of possible deleterious action of such photons on cells of internal tissues. The aim of this study is to compare the sensitivities of skin cells to those of internal organs upon exposure to UV-A. To assess this sensitivity we have determined the UV-A dose-dependent frequency of nuclear DNA breaks detected with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) technique. The materials for the study were macroscopic samples of porcine skin, colon and esophagus. The UV-A dose ranged from 0.1 to 1000 mJ/cm2, which is similar to doses received by cells in regions examined with laser-induced fluorescence or by cells surrounding areas subject to a laser ablation. To reduce the influence of DNA repair processes the tissue samples were kept at a low temperature during the irradiation and were deep frozen immediately after completing the irradiation procedure. The cells of the internal organs are much more susceptible to UV-A-induced breaking of DNA than the skin cells. The percentage fractions and the spatial distributions of the damaged cells and the characteristics of the UV-A dose dependence seem to vary by type of internal organ.
We developed a triple-labeling immunofluorescence technique that simultaneously identifies total DNA (DAPI), DNA damage (antibodies), and dead cells [terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells] and a method that semiquantifies DNA damage in paraffin-embedded tissues. Using this technique in combination with our analysis method, scientists can now simultaneously detect and compare the relative amounts of DNA damage of almost any kind (except single-strand and double-strand breaks), using indirect fluorescent antibody labeling, in both normal and dying cells of different tissues. Simultaneous labeling of DNA damage and dead or TUNEL-positive cells can reduce processing costs and analysis time, and can lead to discoveries concerning how cells die from different DNA damages. We used increasing doses of UV (290 to 400 nm) radiation to create DNA damage in the form of cyclobutane pyrimidine dimers and 6-4 photoproducts that kill some of the cells in 3-dimensional tissue-engineered skin and vaginal samples. We describe a protocol that reliably detects and semiquantifies DNA damage in both normal and apoptotic cells. We show this triple-labeling immunofluorescence technique and analysis method yields linear UV dose response curves for damage to DNA bases that allows semiquantification of cyclobutane pyrimidine dimers and calculation of its repair rate (T=1 and 24 h), whereas TUNEL allows quantification of the number of apoptotic cells. Scientists can now create beautiful fluorescent pictures that simultaneously detect DNA damage in both normal and apoptotic cells to assess and semiquantify the damage to understand better how different insults lead to the cell's demise.
Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks of these procedures, we analyzed the formation and repair of the DNA photoproducts associated with the signature mutations of UVR. Radioimmunoassay was used to quantify the induction and repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts in DNA purified from three reconstructed tissues, EpiDerm(TM) , EpiGingival(TM) and EpiOral(TM) . We observed comparable levels of DNA damage in all tissues immediately after UVR exposure. In contrast, repair was significantly reduced in both oral tissues compared with EpiDerm(TM) . Our data suggest that UVR exposure of oral tissues can result in accumulation of DNA damage and increase the risk for carcinoma and melanoma of the mouth. Because NER is a broad-spectrum defense against DNA damage caused by a variety of agents in addition to UVR, our data suggest that the relatively low NER efficiency observed in oral tissues may have wide-ranging consequences in this highly exposed environment.
Oral lichen planus (OLP) is a chronic inflammatory disease that can significantly affect the patient's quality of life.
We sought to demonstrate the therapeutic efficacy of local ultraviolet (UV) B phototherapy in OLP.
Patients with biopsy-confirmed erosive OLP recalcitrant to previous medical therapy were treated with the TheraLight UV 120-2 system (TheraLight Inc, Carlsbad, CA). Lesions were accessed directly using a flexible fiber guide. Local phototherapy was delivered 3 times a week, with gradual increase in UVB dose every other session. Affected oral mucosa was defined as the area showing erosions or symptomatic reticular lesions. Complete response was defined as reduction of at least 80% in the affected mucosal area, and partial response was defined as a reduction of 50% to 80% in the affected mucosal area. The primary end point was efficacy after 8 weeks of treatment.
Fourteen patients were included in the study. Nine achieved complete response and 5 partial response after 8 weeks. Ten patients were continued on maintenance therapy and were able to maintain their response for another 29 weeks. None of the patients showed any serious side effects from local UVB therapy.
The study was performed in a small series of patients at a single medical center. Further studies with larger patient samples are required to validate our findings.
Local UVB phototherapy may be a promising treatment modality for erosive OLP.
It may be difficult to recognize composite resin restorations that are correctly shade-matched and well-placed by visual and tactile inspection alone--which can make the replacement of an existing resin restoration challenging. Many composite resins fluoresce under UV light, which can help dentists to detect resin material. This article explores a technique that utilizes a UV LED to cause composite resin to fluoresce. A UV/visible light spectrofluorometer was used to measure fluorescence excitation and emission maxima of 14 composite resin brands. Control samples of dentin and enamel were measured in a similar manner. Subsequently, each brand of composite resin was placed in extracted teeth and relative fluorescence was assessed. The composite resins were then removed and each tooth was inspected using UV light to detect remaining resin. Results from this study indicated that the optimal excitation wavelength was 385-395 nm, while 460 nm was determined to be the mean emission maxima. This study revealed three types of resin: highly fluorescent, moderately fluorescent, and weakly fluorescent. In each instance, the UV light revealed the presence of resin after all resin was believed to have been removed. Based on the results of this study, the use of UV illumination can be a useful technique for determining if composite resin has been removed completely.
Patients with photosensitive dermatologic and systemic diseases often question the ultraviolet light (UVL) output of household lighting sources. Such individuals have increasing concern about potential UVL exposure from energy-efficient compact fluorescent lamps (CFL), as little data have been presented concerning their UVL output. The objective was to compare, via pilot study, the levels of ultraviolet A (UVA) and ultraviolet B (UVB) leak between residential lighting sources. Equivalent wattage CFL, incandescent and halogen bulbs were purchased from local retailers in Oklahoma City, Oklahoma, USA. The UVA and UVB outputs of these sources were measured under controlled conditions at 10, 25, 50, 100 and 150 cm away from the light source using an IL-1700 research radiometer equipped with UVA and UVB detectors. Negligible UVB and UVA was detected at 100 and 150 cm. Therefore, data were analysed from measurements at 10, 25 and 50 cm only. The results demonstrated UVA leak highest from incandescent and halogen bulbs, and UVB leak highest from CFL. The overall UVA/UVB leak was lowest from CFL shielded during the manufacturing process. In conclusion, patients with photosensitivity have choices depending on their relative risk from different UVL wavelength spectra. UVB exposure risk may be reduced the greatest by utilising CFL with manufacturer-provided shields.
The use of optical radiation in the so-called light-assisted tooth bleaching procedures has been suggested to enhance the oxidizing effect of the bleaching agent, hydrogen peroxide. Documentation is scarce on the potential adverse effects of bleaching products and on optical exposure risks to eyes and skin. The efficacy of seven bleaching products with or without simultaneous use of seven different bleaching lamps was investigated using extracted human teeth. The bleaching effect was determined immediately after treatment and one week later. Tooth surfaces were examined for adverse alterations after bleaching using a scanning electron microscope. Source characteristics of eight lamps intended for tooth bleaching were determined. International guidelines on optical radiation were used to assess eye and skin exposure hazards due to UV and visible light emission from the lamps. Inspection of teeth one week after bleaching showed no difference in efficacy between teeth bleached with or without irradiation for any of the products. Scratches, probably from the cleaning procedure were frequently seen on bleached enamel irrespective of irradiation. Maximum permissible exposure time (t(max)) and threshold limit values were exceeded for about half the bleaching lamps investigated. One lamp exceeded t(max) even for reflected blue light within the treatment time. This lamp also exceeded t(max) values for UV exposure. The lamps were classified as "low risk" and as borderline to "moderate risk" according to a relevant lamp standard.
Cutaneous malignant melanoma (CMM) has been increasing at a steady exponential rate in fair-skinned, indoor workers since before 1940. A paradox exists between indoor and outdoor workers because indoor workers get three to nine times less solar UV (290-400 nm) exposure than outdoor workers get, yet only indoor workers have an increasing incidence of CMM. Thus, another "factor(s)" is/are involved that increases the CMM risk for indoor workers. We hypothesize that one factor involves indoor exposures to UVA (321-400 nm) passing through windows, which can cause mutations and can break down vitamin D(3) formed after outdoor UVB (290-320 nm) exposure, and the other factor involves low levels of cutaneous vitamin D(3). After vitamin D(3) forms, melanoma cells can convert it to the hormone, 1,25-dihydroxyvitamin D(3), or calcitriol, which causes growth inhibition and apoptotic cell death in vitro and in vivo. We measured the outdoor and indoor solar irradiances and found indoor solar UVA irradiances represent about 25% (or 5-10 W/m(2)) of the outdoor irradiances and are about 60 times greater than fluorescent light irradiances. We calculated the outdoor and indoor UV contributions toward different biological endpoints by weighting the emission spectra by the action spectra: erythema, squamous cell carcinoma, melanoma (fish), and previtamin D(3). Furthermore, we found production of previtamin D(3) only occurs outside where there is enough UVB. We agree that intense, intermittent outdoor UV overexposures and sunburns initiate CMM; we now propose that increased UVA exposures and inadequately maintained cutaneous levels of vitamin D(3) promotes CMM.
Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway) and human skin (EpiDerm) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage.
An ultraviolet-light dental camera was used to disclose plaque in relation to directly bonded plastic orthodontic brackets. No disclosing solution was used. The reestablishment of plaque patterns 14 days after a prophylaxis and in the presence of the brackets was noted. A further cleaning after debonding removed the plaque, which returned to the base line pattern within 14 days. Small resin remnants left during debonding did not form foci for plaque growth and spread over a 6-month observation period.
Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized
by persistent angiogenesis. The possibility was tested that interleukin-8 (IL-8), which is a cytokine that is chemotactic
for lymphocytes and neutrophils, is also angiogenic. Human recombinant IL-8 was potently angiogenic when implanted in the
rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells. Angiogenic activity present
in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes
was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha. An IL-8 antisense oligonucleotide specifically
blocked the production of monocyte-induced angiogenic activity. These data suggest a function for macrophage-derived IL-8
in angiogenesis-dependent disorders such as rheumatoid arthritis, tumor growth, and wound repair.
We report the first study of the application of excimer lasers in dentistry for the treatment of dental root canals. High-energy ultraviolet (UV) radiation emitted by an XeCl excimer laser (308 nm) and delivered through suitable optical fibers can be used to remove residual organic tissue from the canals. To this aim, UV ablation thresholds of dental tissues have been measured, showing a preferential etching of infiltrated dentin in respect to healthy dentin, at laser fluences of 0.5-1.5 J/cm2. This technique has been tested on extracted tooth samples, simulating a clinical procedure. Fibers of decreasing core diameters have been used to treat different sections of the root canal down to its apical portion, resulting in an effective, easy, and fast cleaning action. Possible advantages of excimer laser clinical applications in respect to usual procedures are also discussed.
EpiDerm (MatTek Co., MA) is a reconstituted human skin equivalent which exhibits morphological and growth characteristics similar to human skin. This model has previously been utilized to evaluate the cytotoxicity and irritant potential of various cosmetic and household products. In this study, we show for the first time that EpiDerm can be used successfully to evaluate the genotoxicity of different types of known carcinogenic agents such as benzo[a]pyrene (BaP), ultraviolet B radiation (UVB), ultraviolet A radiation (UVA), and psoralen-ultraviolet A radiation (PUVA) at the molecular level. The topical application of 50 microg/cm2 BaP to EpiDerm resulted in the accumulation of BaP-DNA adducts and c-fos and p53 proteins as evidenced by immunohistochemical localization. Similarly, exposure to UVB (50 mJ/cm2) and UVA (2.5 J/cm2) enhanced the epidermal expression of c-fos and p53 proteins in the human skin equivalent. PUVA treatment of EpiDerm, however, resulted in the formation of both DNA-8-MOP adducts and augmented expression of c-fos and p53 proteins. Most of these changes reached a peak 8 h after the treatments except in the case of UVA where maximum changes in the expression of c-fos and p53 proteins were observed 24 h after treatment. These results are similar to those previously reported in human and murine skin following exposure to BaP, UVB, UVA, or PUVA indicating that human skin equivalents can be used as a convenient and cost-effective alternative to animal testing for assessing the genotoxicity and mechanism of action of mutagens/carcinogens in human skin.
In order to gain further understanding of the role of chemokines in healthy oral mucosa, we analyzed mRNA expression of the alpha (CXC)-family chemokines IL-8 and GROgamma as well as of the beta (CC)-family chemokines MIP-1alpha, MIP-1beta and MCP-1 in twenty young and healthy subjects with good oral hygiene. Twenty biopsies were taken from clinically healthy oral mucosa before surgical removal of impacted wisdom teeth. In addition, five biopsies from patients presenting with specific oral lesions were studied. RNA was purified, quantitated and utilized as substrate for competitive reverse transcription-polymerase chain reaction (RT-PCR). In healthy tissue, IL-8 and MCP-1 mRNA was constitutively expressed in all biopsies, whereas GROgamma, MIP-1alpha, and MIP-1beta were significantly lower. These findings suggest that IL8 and MCP-1 play a significant role in oral tissue homeostasis. The few samples from pathological conditions encourage exploring diseased tissue in more detail.
Ultraviolet irradiation inhibits the proliferative responses of lymphoid cells to mitogens and alloantigens by inactivation of T lymphocytes and antigen-presenting cells. Its immunosuppressive capacity led to the introduction of UV irradiation into clinical practice for the treatment of dermatologic manifestations of chronic graft-versus-host disease. The cumulative experience with psoralen-UV-A rays in the treatment of cutaneous and oral graft-versus-host disease was the incentive for the application of oral UV-B rays in 2 patients with oral graft-versus-host disease signs and symptoms after allogeneic marrow transplantation. Intraoral UV-B irradiation (0.02 mJ/cm(2)) was administered 2 or 3 times per week on an ambulatory basis; the dose was increased by 0. 02 mJ/cm(2) every fourth session. Both patients responded early and satisfactorily, displaying only minimal side effects at a relatively low cumulative dose. Intraoral UV-B proved a valuable modality in the treatment of resistant chronic oral graft-versus-host disease.
We studied the p53 mutational spectra of 34 lip and 60 intra-oral squamous-cell carcinomas and examined possible etiological and prognostic correlations for these tumor sites. For the p53 analysis of exons 5-8, we used PCR/TGGE screening followed by DNA sequencing. Mutations were found in 18/34 (53%) lip and 22/60 (38%) intra-oral carcinomas. The p53 mutational spectrum of the intra-oral carcinomas comprised transitions and transversions in nearly equal frequency (11 to 10). In comparison, transitions were 3.5 times more frequent than transversions (14 to 4) in carcinomas of the lip. The predominant types of base change found in intra-oral tumors were G:C-to-T:A transversions and G:C-to-A:T transitions (32% each), while in lip tumors G:C-to-A:T transitions (70%) were the most frequent. The rate of lip tumors with mutations was higher in non-smokers (8/13) than in smokers (9/20). In contrast, p53 mutations in intra-oral tumors clustered in smokers (18/47 vs. 2/10). G:C-to-T:A transversions, regarded as tobacco smoke-associated in lung cancer, were found in 2 moderate and 4 heavy smokers with intra-oral cancer. This base substitution was found in none of our lip cancers. In lip tumors, a high rate of mutations occurred at dipyridine sites (13/18); among these were 8 C-to-T transitions and 1 CC-to-TT tandem base transition. These changes are characteristic of DNA damage caused by UV light. The presence of mutational events at the DNA-binding surface of the p53 protein may correlate with poor clinical outcome. However, we could not find any statistically significant correlations between p53 status and survival. Only the recurrence-free interval was significantly shortened in cases with mutations affecting residues of the DNA-binding surface of the p53 protein.
There is increasing knowledge about the hazards of solar and ultraviolet (UV) radiation to humans. Although people spend a significant time in cars, data on UV exposure during traveling are lacking. The aim of this study was to obtain basic information on personal UV exposure in cars.
UV transmission of car glass samples, windscreen, side and back windows and sunroof, was determined. UV exposure of passengers was evaluated in seven German middle-class cars, fitted with three different types of car windows. UV doses were measured with open or closed windows/sunroof of Mercedes-Benz E 220 T, E 320, and S 500, and in an open convertible car (Mercedes-Benz CLK). Bacillus subtilis spore film dosimeters (Viospor) were attached to the front, vertex, cheeks, upper arms, forearms and thighs of 'adult' and 'child' dummies.
UV wavelengths longer than >335 nm were transmitted through car windows, and UV irradiation >380 nm was transmitted through compound glass windscreens. There was some variation in the spectral transmission of side windows according to the type of glass. On the arms, UV exposure was 3-4% of ambient radiation when the car windows were shut, and 25-31% of ambient radiation when the windows were open. In the open convertible car, the relative personal doses reached 62% of ambient radiation.
The car glass types examined offer substantial protection against short-wave UV radiation. Professional drivers should keep car windows closed on sunny days to reduce occupational UV exposure. In individuals with polymorphic light eruption, produced by long-wave UVA, additional protection by plastic films, clothes or sunscreens appears necessary.
Lichen planus is a difficult-to-treat chronic inflammatory disorder that affects mucous membranes, causing inanition, halitosis, and dyspareunia.
To evaluate the novel use of low-dose 308-nm excimer laser radiation for the treatment of symptomatic oral lichen planus (OLP).
A single-center, before-after trial.
Academic clinical research center.
Nine patients with symptomatic, biopsy-proven OLP, unresponsive to conventional therapies, were recruited from the dermatology clinics of the Massachusetts General Hospital in Boston. Eight participants completed the entire study, and 1, despite early improvement, did not complete the study because of hospitalization for an unrelated reason. Intervention With a narrow, fiberoptic handpiece to target precisely only diseased sites, 308-nm excimer laser radiation was delivered at an initial dose of 100 mJ/cm(2) once a week.
A visual analog scale was used to grade subjective disease severity. Clinical improvement was graded in quartiles as follows: poor (<25%), fair (25%-50%), good (51%-75%), and excellent (>75%). Follow-up visits occurred for up to 18 months. A paired t test was performed to evaluate efficacy of treatment.
Treatments were painless and well tolerated. Five patients demonstrated overall excellent clinical and subjective improvement after 7 treatments. Two participants with nonerosive OLP were deemed fair responders. The only poor responder in the study also had chronic active hepatitis C infection. Overall improvement was statistically significant (P<.05), and for the responders, remission times ranged from 2 to 17 months. Conclusion Low-dose treatment with the excimer 308-nm laser can be very effective in treating symptomatic and especially erosive OLP, an otherwise notoriously difficult-to-control disease.
Discussions of risks and implications of cutaneous exposure to indoor lighting, including hypothetical contribution to causality of melanoma, have mainly concentrated on ultraviolet (UV) A and B (UVA, UVB) spectral emissions from fluorescent bulbs. Only studies of quartz halogen lamps have suggested that users might sustain UVC-induced injury. Examination of light sources in the home and school of a child with xeroderma pigmentosum revealed that several different types emitted surprising levels of UV. Our purpose was to assess the extent of UV emissions from a variety of commonly used light sources to identify potential dermatological risks. UV and visible spectral emissions of commercially obtained lamps of several types were measured using a calibrated spectral radiometer traceable to the National Institute of Standards and Technology. Indoor light sources including fluorescent, quartz halogen and even tungsten filament incandescent lamps provided UVA, UVB and sometimes UVC emissions. Intensities of some emissions were of similar magnitude to those in sunlight. Chronic exposure to indoor lighting may deliver unexpected cumulative UV exposure to the skin and eyes. Patients with UV-exacerbated dermatoses should be cautioned about potential adverse reactions from indoor lighting.
The high and steadily increasing incidence of ultraviolet-B (UV-B)-induced skin cancer is a problem recognized worldwide. UV introduces different types of damage into the DNA, notably cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts (6-4PPs). If unrepaired, these photolesions can give rise to cell death, mutation induction, and onset of carcinogenic events, but the relative contribution of CPDs and 6-4PPs to these biological consequences of UV exposure is hardly known. Because placental mammals have undergone an evolutionary loss of photolyases, repair enzymes that directly split CPDs and 6-4PPs into the respective monomers in a light-dependent and lesion-specific manner, they can only repair UV-induced DNA damage by the elaborate nucleotide excision repair pathway.
To assess the relative contribution of CPDs and 6-4PPs to the detrimental effects of UV light, we generated transgenic mice that ubiquitously express CPD-photolyase, 6-4PP-photolyase, or both, thereby allowing rapid light-dependent repair of CPDs and/or 6-4PPs in the skin. We show that the vast majority of (semi)acute responses in the UV-exposed skin (i.e., sunburn, apoptosis, hyperplasia, and mutation induction) can be ascribed to CPDs. Moreover, CPD-photolyase mice, in contrast to 6-4PP-photolyase mice, exhibit superior resistance to sunlight-induced tumorigenesis.
Our data unequivocally identify CPDs as the principal cause of nonmelanoma skin cancer and provide genetic evidence that CPD-photolyase enzymes can be employed as effective tools to combat skin cancer.
There is a continuously growing interest in medical applications of ultraviolet radiation (UV-A and long-wavelength UV-B) especially for laser surgery, phototherapy and photodiagnostics of human internal organs. UV-B and UV-A radiation is potentially mutagenic, however, there has been very little information published to date concerning the significance of possible deleterious action of such photons on cells of internal tissues. The aim of this study is to compare the sensitivities of skin cells to those of internal organs upon exposure to UV-A. To assess this sensitivity we have determined the UV-A dose-dependent frequency of nuclear DNA breaks detected with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) technique. The materials for the study were macroscopic samples of porcine skin, colon and esophagus. The UV-A dose ranged from 0.1 to 1000 mJ/cm2, which is similar to doses received by cells in regions examined with laser-induced fluorescence or by cells surrounding areas subject to a laser ablation. To reduce the influence of DNA repair processes the tissue samples were kept at a low temperature during the irradiation and were deep frozen immediately after completing the irradiation procedure. The cells of the internal organs are much more susceptible to UV-A-induced breaking of DNA than the skin cells. The percentage fractions and the spatial distributions of the damaged cells and the characteristics of the UV-A dose dependence seem to vary by type of internal organ.
UV radiation affects human health. Human exposure to UV radiation causes a few beneficial health effects like vitamin D3 formation but it causes many detrimental health effects: sunburn, ocular damage, photoaging, immune suppression, DNA damage and skin cancer. In countries with fair-skinned populations, skin cancer is the most diagnosed of all cancers. In the United States in 2002, there were over one million new skin cancer cases. That means one out of every 285 people got skin cancer. Skin cancer of fair-skinned individuals is increasing at an alarming rate (4-6% per year) around the world and has now reached so-called "pandemic" proportions. Thus, it is important to know what UV doses people around the world get throughout their lives. This review covers how the outdoor UV doses are weighted for different biological effects, the most commonly used measuring devices for terrestrial and personal UV doses, the natural and other effects on terrestrial and personal UV doses, the time people spend outside, their ambient exposures and the terrestrial and personal UV doses of adult outdoor and indoor workers as well as children and adolescents around the world. Overall, outdoor-working adults get about 10%, while indoor-working adults and children get about 3% (2-4%) of the total available annual UV (on a horizontal plane). People's UV doses increase with increasing altitude and decreasing latitude; most indoor-working adult Europeans get 10,000-20,000 J/m2 per year, Americans get 20,000-30,000 J/m2 per year and Australians are estimated to get 20,000-50,000 J/m2 per year (excluding vacation, which can increase the dose by 30% or more).
Genistein, the most abundant isoflavone of the soy derived phytoestrogen compounds, is a potent antioxidant and inhibitor of tyrosine kinase. We previously reported the antiphotocarcinogenic effects of genistein in SKH-1 murine skin, including its capacity for scavenging reactive oxygen species, inhibiting photodynamic DNA damage and downregulating UVB(ultra violet B)-induced signal transduction cascades in carcinogenesis. In this study we elucidate genistein's photoprotective efficacy within the context of full thickness human reconstituted skin relative to acute challenges with ultraviolet-B irradiation. Skin samples were pre-treated with three concentrations of genistein (10, 20 and 50 microM) 1 h prior to UVB radiation at 20 and 60 mJ/cm2. Proliferating cell nuclear antigen (PCNA) and pyrimidine dimer (PD) expression profiles were localized using immunohistochemical analysis on paraffin embedded samples 6 and 12 h post UVB exposure. Genistein dose dependently preserved cutaneous proliferation and repair mechanics at 20 and 60 mJ/cm2, as evidenced by the preservation of proliferating cell populations with increasing genistein concentrations and noticeable paucity in PCNA immunoreactivity in the absence of genistein. Genistein inhibited UV-induced DNA damage, evaluated with PD immunohistochemical expression profiles, demonstrated an inverse relationship with increasing topical genistein concentrations. Irradiation at 20 and 60 mJ/cm2 substantially induced PD formation in the absence of genistein, and a dose dependent inhibition of UVB-induced PD formation was observed relative to increasing genistein concentrations. Collectively all genistein pre-treated samples demonstrated appreciable histologic architectural preservation when compared with untreated specimens. These findings represent a critical link between our animal and cell culture studies with those of human skin and represent the first characterization of the dynamic alterations of UV-induced DNA damage and proliferating cell populations relative to pretreatment with genistein in human reconstituted skin. The implications of our findings serve as compelling validation to our conclusions that genistein may serve as a potent chemopreventive agent against photocarcinogenesis.
The objective of the present study was to study the role of reactive oxygen species (ROS) in UVB induced cyclobutane pyrimidine dimer (CPD) formation in human keratinocytes, and to examine the modulating activity of low molecular weight antioxidants. To demonstrate the involvement of ROS, we examined the protective capacity of alpha-tocopherol, tempamine, and diethyldithiocarbamate (DDC) on CPD formation in intact cells and naked DNA. HaCaT cells and naked DNA in water solution were irradiated with UVB in the presence of the antioxidants and CPD was determined by ELISA. We found that all three antioxidants provided protection against UVB induced CPD formation. The protection was observed in intact cells only and not in naked DNA. Since some of the tested antioxidants do not possess UV absorbing qualities, our findings suggest that in a cellular environment ROS play a role in CPD formation.
Phototherapy has a profound immunosuppressive effect and is widely used for the treatment of immune mediated skin diseases. Phototherapy is able to inhibit immediate type hypersensitivity reaction in the skin. Intranasal phototherapy is a new approach for treatment of allergic rhinitis. In two open studies, 308 nm excimer laser and topical PUVA therapy efficiently inhibited clinical symptoms of allergic rhinitis. In a randomized, double-blind study combined low dose UVB, low dose UVA and visible light proved to be effective in reducing symptom scores for sneezing, rhinorrhea, nasal itching and the total nasal score in ragweed allergic patients. Mechanism of action of phototherapy is complex, it reduces the antigen presenting capacity of dendritic cells, induces apoptosis of immune cells and inhibits synthesis and release of pro-inflammatory mediator from several cell types. Therefore, intranasal phototherapy may represent an alternative treatment of allergic rhinitis and other inflammatory and immune mediated mucosal diseases.
Rhinophototherapy has been shown to be effective in the treatment of allergic rhinitis. Considering that phototherapy with ultraviolet light (UV) induces DNA damage, it is of outstanding importance to evaluate the damage and repair process in human nasal mucosa.
We have investigated eight patients undergoing intranasal phototherapy using a modified Comet assay technique and by staining nasal cytology samples for cyclobutane pyrimidine dimers (CPDs), which are UV specific photoproducts.
Immediately after last treatment Comet assay of nasal cytology samples showed a significant increase in DNA damage compared to baseline. Ten days after the last irradiation a significant decrease in DNA damage was observed compared to data obtained immediately after finishing the treatment protocol. Difference between baseline and 10 days after last treatment was not statistically significant. Two months after ending therapy, DNA damage detected by Comet assay in patients treated with intranasal phototherapy was similar with that of healthy individuals. None of the samples collected before starting intranasal phototherapy stained positive for CPDs. In all samples collected immediately after last treatment strong positive staining for CPDs was detected. The number of positive cells significantly decreased 10 days after last treatment, but residual positive staining was present in all the examined samples. This finding is consistent with data reported in skin samples after UV irradiation. Cytology samples examined two months after ending therapy contained no CPD positive cells.
Our results suggest that UV damage induced by intranasal phototherapy is efficiently repaired in nasal mucosa.
Simultaneous detection and semi-quantification of DNA damage in normal and apoptotic cells: triple-immunofluorescent labeling using DAPI, antibodies, and TUNEL
- Agrawal
Agrawal, A. and D. E. Godar (2012) Simultaneous detection and
semi-quantification of DNA damage in normal and apoptotic cells:
triple-immunofluorescent labeling using DAPI, antibodies, and
TUNEL. Appl. Immunohistochem. Mol. Morphol. 20, 402-409.
UVB-induced cytokine release from human oral and skin tis-sue equivalents
- J Breger
- L Baeva
- A Agrawal
- E Shindell
- D E Godar
Breger, J., L. Baeva, A. Agrawal, E. Shindell, and D. E. Godar (2012) UVB-induced cytokine release from human oral and skin tis-sue equivalents. Photochem. Photobiol. DOI: 10.1111/php.12030. Dec 15. [Epub ahead of print]
Skin cancer facts. Melanoma Available at: http://www.skincancer.org/skin-cancer-information/melanoma
Skin cancer foundation (2012) Skin cancer facts. Melanoma. Available at: http://www.skincancer.org/skin-cancer-information/melanoma.
Assessed on 12 September 2012.
Food and Drug Administration . 21 CFR Part 1040 (Docket No. 82N-0188) Sunlamp Products ; Performance Standard -Final Rule
Department of Health and Human Services, Food and Drug Administration. 21 CFR Part 1040 (Docket No. 82N-0188). Sunlamp Products ; Performance Standard -Final Rule. Federal Register, Vol. 50,
No. 173, Friday, 6 September 1985.
Cogliano and WHO International Agency for Research on Cancer Monograph Working Group (2009) A review of human carcinogenspart D: Radiation
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- R Baan
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- Y Grosse
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- V Bouvard
- L Benbrahim-Tallaa
- N Guha
- C Freeman
- L Galichet
El Ghissassi, F., R. Baan, K. Straif, Y. Grosse, B. Secretan, V.
Bouvard, L. Benbrahim-Tallaa, N. Guha, C. Freeman, L. Galichet,
V. Cogliano and WHO International Agency for Research on Cancer
Monograph Working Group (2009) A review of human carcinogenspart D: Radiation. Lancet Oncol., 10, 751-752.
Food and Drug Administration. 21 CFR Part 1040 (Docket No. 82N-0188)
Department of Health and Human Services, Food and Drug Administration. 21 CFR Part 1040 (Docket No. 82N-0188). Sunlamp Products; Performance Standard -Final Rule. Federal Register, Vol. 50,
No. 173, Friday, 6 September 1985.
UVB-induced cytokine release from human oral and skin tissue equivalents
- Breger
p53 mutational spectra are different between squamous-cell carcinomas of the lip and the oral cavity
- Ostwald