Article

Risk of oral cancer and tooth whitening products

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Abstract

Tooth whitening products (TWP) containing hydrogen peroxide (HPO) or carbamide peroxide (CPO) were evaluated in relation to potential oral cancer risk from their use. HPO is genotoxic in vitro, but such activity is not expressed in vivo. The genotoxic risk of HPO exposure of the oral mucosa encountered from TWP use is likely therefore to be vanishingly small. Available animal data on the carcinogenicity of HPO are of limited relevance to risk assessment of oral hazard of HPO exposure from TWP, and where relevant, do not indicate that there is an increased oral cancer risk for people using TWP. Clinical data on HPO-containing TWP only show evidence of mild, transient gingival irritation and tooth sensitivity, with no evidence for the development of preneoplastic or neoplastic oral lesions. Exposures to HPO received by the oral cavity, including areas commonly associated with oral cancer, are exceedingly low and do not plausibly pose a risk for the promotion of initiated cells or for induction of co-carcinogenic effects in conjunction with cigarette smoke or alcohol. The use of TWP was concluded not to pose an increased risk for oral cancer in alcohol abusers and/or heavy cigarette smokers. Furthermore, TWP were concluded to be safe for use by all members of the population, including potential accidental use by children.

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... It is a procedure with an ever-increasing popularity, especially with younger patients. The debate about the potential carcinogenic and damaging effects of teeth whitening or bleaching procedures that use carbamide peroxide has been a lengthy one (1)(2)(3), and there is still inconclusive data regarding the issue. In some countries all substances containing carbamide peroxide have been banned ACTA STOMATOLOGICA CROATICA www.ascro.net ...
... metikom i prodaja tih proizvoda je zabranjena (5). Predvidljivost postupka i njegove moguće štetne posljedice -koliko god bile male -detaljno su istražene (1)(2)(3). Do danas nema objavljenih istraživanja o mogućem štetnom utjecaju VivaStyle (Ivoclar Vivadent, Schaan, Liechtenstein) sustava za izbjeljivanje zuba, koji se temelji na 10 %-tnom karbamidnom peroksidu, na zdravlje parodonta, točnije na gingivalni integritet. Zbog toga smo pokušali obaviti istraživanje na dobrovoljcima s klinički zdravim parodontnim tkivom kako bismo mogli detektirati mogući štetni utjecaj odobrenog sustava za izbjeljivanje zuba na marginalna parodontna tkiva. ...
... In the European Union, the bleaching agents are considered to be cosmetics, and the sale of these products is prohibited (5). The predictability of the procedures and their potential damaging consequences, however small they may be, has been studied extensively (1)(2)(3). There are no studies that have surveyed potential deteriorating effect of VivaStyle (Ivoclar Vivadent, Schaan, Liechtenstein) -10% carbamide peroxide teeth whitening system on periodontal health, more precisely, gingival integrity. ...
Article
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The aim of this study was to examine the effects of a 10% carbamide peroxide bleaching gel (VivaStyle, Ivoclar Vivadent, Schaan, Liechtenstein) on periodontal health. Ten participants, 22 to 29 years of age, with clinically healthy periodontal tissues and a wish to change the shade of their teeth, participated in this study. Subjects were treated with 10% carbamide peroxide for one hour daily during 12 days. The volunteers were instructed to keep a diary of possible disturbances during the teeth whitening procedure. At baseline, on 6th and on 12th day API score and PBI score were measured and clinical photograph of teeth in intercuspidation relation was taken. All teeth demonstrated change of at least one shade. There was no change in either plaque accumulation, or gingival inflammation during the teeth whitening procedure. This teeth whitening procedure seems not to have any influence on the periodontal health.
... Enligt SCCP (1) visar studier på att celler anpassar sig till att reparera DNA skador orsakade av oxidanter; å andra sidan är det viss evidens för att väteperoxid kan inhibera reparationen av DNA-lesioner tillfogade av andra typer av reaktiva kemikalier (1). Det förekommer misstankar om att väteperoxid kan fungera som en promotor för cancerceller (4) och man har också sett att väteperoxid är genotoxiskt in vitro men att en sådan aktivitet inte uttrycks in vivo (14). Studier visar på att i de kliniska situationerna, genererar inte de dagliga små doserna som fås vid blekning, några akuta eller toxiska effekter. ...
... Genotoxicitet och cancerogenitet sker alltså bara vid högre doser som aldrig uppnås under tandläkarbehandling (10). Därmed blir den genotoxiska risken vid tandblekning med väteperoxid mycket liten (14). Inte heller ökar den cancerogena risken vid rökning eller alkoholintag i samband med blekning, då väteperoxidexponeringen till munhålan är liten (14). ...
... Därmed blir den genotoxiska risken vid tandblekning med väteperoxid mycket liten (14). Inte heller ökar den cancerogena risken vid rökning eller alkoholintag i samband med blekning, då väteperoxidexponeringen till munhålan är liten (14). Dock har väteperoxid en välkänd potential att orsaka irritationer, och därmed finns det risk för överdriven toxisk effekt vid tillstånd som tidigare vävnadsskador eller frekventa intag av alkohol och tobak vid samtidig exponering av blekningsprodukter (1). ...
... Some studies [5,7,8], however, report that these side effects are transient and can be recovered from after treatment. Safety for exposure to a long-term H 2 O 2 bleaching agent has also been a concern in more recent studies [9,10]. H 2 O 2 generates free radicals, especially hydroxyl radical, in oxidative reactions; free radicals are considered genotoxic and carcinogenic [11,12]. ...
... The safety of H 2 O 2 tooth bleaching is still controversial: its genotoxicity and carcinogenicity are under active discussion [9,10]. Diaz-Llera et al. showed that 0.34-1.35 ...
... μM of H 2 O 2 induced hypoxanthine guanine phosphoribosyltransferase (HPRT) mutation both in vitro and in vivo [31]. High-dose H 2 O 2 was reported to be mildly carcinogenic for the duodenum of catalasedeficient mice [9]. In another report, 1% H 2 O 2 (~0.3 M) in drinking water induced forestomach tumors in rats [10]. ...
Article
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Background Hydrogen peroxide (H2O2)-based tooth bleaching reagents have recently increased in popularity and controversy. H2O2 gel (3%) is used in a Nightguard for vital bleaching; transient tooth sensitivity and oral mucosa irritation have been reported. Genotoxicity and carcinogenicity have also been significant concerns. Methods We used primary cultured normal human oral keratinocytes (NHOKs) as an in vitro model to investigate the pathological effects to mitochondria functions on human oral keratinocytes exposed to different doses of H2O2 for different durations. Results An MTT assay showed compromised cell viability at a dose over 5 mM. The treatments induced nuclear DNA damage, measured using a single-cell gel electrophoresis assay. A real-time quantitative polymerase chain reaction showed H2O2 induced significant increase in mitochondrial 4977-bp deletion. Mitochondrial membrane potential and apoptosis assays suggested that oxidative damage defense mechanisms were activated after prolonged exposure to H2O2. Reduced intracellular glutathione was an effective defense against oxidative damage from 5 mM of H2O2. Conclusion Our study suggests the importance for keratinocyte damage of the dose and the duration of the exposure to H2O2 in at-home-bleaching. A treatment dose ≥100 mM directly causes severe cytotoxicity with as little as 15 min of exposure.
... Previous clinical research of the side-effects of dental bleaching has mostly focused on postoperative sensitivity and gum irritation, while data on genotoxicity are lacking (17). Although gum irritation occurs frequently, it is not considered a risk factor for development of oral cancer (17). ...
... Previous clinical research of the side-effects of dental bleaching has mostly focused on postoperative sensitivity and gum irritation, while data on genotoxicity are lacking (17). Although gum irritation occurs frequently, it is not considered a risk factor for development of oral cancer (17). There is also no evidence of any cancer-promoting activity of hydrogen peroxide in smokers and people who consume large amounts of alcohol (18). ...
Article
Aim: To analyze the genotoxic effect of two hydrogen peroxide-containing bleaching products on oral mucosal cells. The research was conducted on 22 individuals divided into two groups. Group 1 used ZOOM2 and group 2 the Opalescence BOOST bleaching agent. Specimens of the gingival and the upper lip mucosa were obtained before, immediately after, and 72 h after the bleaching procedure and were analyzed using a micronucleus test. Seventy-two hours after bleaching treatment with BOOST, samples collected from the oral mucosa exhibited a statistically significant increase of all genotoxicity markers, with large effect sizes (Cohen's d>0.8) observed in the total number of micronuclei (MN), number of cells with 3+ MN, karyolysis and bi-nuclear cells. ZOOM2 treatment showed a significant increase, with medium-to-large effect sizes, in the number of cells with 1 MN, karyolysis, nuclear buds and bi-nuclear cells. Both preparations demonstrated potential genotoxic effects.
... Ayrıca bu ürünlerle ilgili yapılan araştırmaların kısıtlı sayıda olması ve genellikle ticari firmaların desteğiyle düzenlenmesi nedeniyle, oral dokular açısından güvenliği hala tartışma konusudur. [18][19][20][21][22] ii. Hekim Kontrolünde Ev Tipi Beyazlatma Hekim, tedavinin endikasyonunu değerlendirir, başlangıç rengini ve başlangıç klinik fotoğraflarını kaydeder. ...
... Ürenin varlığı, ajana daha uzun bir raf ömrü kazandırmakta ve hidrojen peroksidin salınımını yavaşlatmaktadır. 22 26 Literatürde bu konuda çok farklı sonuçlar veren çalışmalar mevcuttur. Güncel sistematik derleme ve literatür meta analizlerinde ofis tipi beyazlatmada ışık kullanımının beyazlatmanın etkinliğine ve diş hassasiyetine olan etkisi değerlendirilmiştir. ...
... 타낼 수 있고, 주변 살아있는 세포를 파괴할 수 있어서 발암 성이 있다고 알려져 왔다. [11][12][13][14] 따라서 전문가 미백술에 사용 되는 미백제인 고농도의 과산화수소를 대량 섭취하면 염증 을 일으킬 수 있고 조직의 병적인 변화를 야기할 수 있을 것 이라는 주장이 제기되었다. 15 ...
Article
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This study evaluated the safety of an office bleaching gel (RemeWhite, Remedent Inc., Deurle, Belgium) containing 30% hydrogen peroxide. 37 volunteers were received office bleaching with the RemeWhite for 3 times at one visit, total 2 visits. As control group, the same gel in which hydrogen peroxide was not included was applied to 34 volunteers with the same protocol. There was no difference between experimental group and control group using electric pulp test. In the result of gingival inflammation index and tooth sensitivity test, there was mild pain response in experimental group but it disappeared as time went by. Therefore, safety of the office bleaching gel containing 30% hydrogen peroxide was confirmed.
... Overall, tooth-whitening products are safe for use by the human population. 20 of OTC products is their low cost. Do they all remove intrinsic stains? ...
... [1][2][3][4][5][6] The use of high concentrations of hydrogen peroxide or carbamide peroxide on tooth whitening could affect tooth enamel, 7 and it also could have several secondary effects. [8][9][10][11] In addition, toxic effects of hydrogen peroxide have been evidenced 'in vitro'. [12][13][14] Future technologies for whitening teeth could involve the use of activating agents to enhance the performance of hydrogen peroxide. ...
Article
Carbamide peroxide and hydrogen peroxide have been used as tooth whitening agents. The aim of this paper was to determine the efficiency of several enzyme-containing whitening systems. A method to determine the rate of 'in vitro' tetracycline whitening was also developed. We determined the tetracycline whitening ability of carbamide peroxide and hydrogen peroxide, and the influence of peroxidase and lactoperoxidase on this tetracycline whitening rate. High peroxidase and lactoperoxidase concentrations increased the rate of tetracycline decoloration obtained with carbamide peroxide or hydrogen peroxide. The decoloration rate observed was lower when the glucose/glucose oxidase system was used to generate hydrogen peroxide 'in situ'. The presence of peroxidase increased the decoloration rate of extracted teeth obtained with carbamide. Enzymes such as peroxidase could be used as whitening catalysts to increase the rate of tetracycline decoloration.
... Hydrogen peroxide and carbamide peroxide have been used for debridement during endodontic therapy, in mouth rinses to reduce plaque in individuals with gingivitis, and for treatment of periodontal diseases [13,14]. [15,16]. ...
... Vital bleaching of teeth with hydrogen peroxide under controlled clinical conditions has widely been used to lighten teeth. Nevertheless several reports of gingival irritation and ulceration in some patients suggest that bleaching agents, under certain cir- cumstances, promote toxic effects on oral cells and in human gingival fibroblasts [38,39]. ...
Article
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In the process of bleaching vital, discolored teeth, low concentrations of hydrogen peroxide (H2O2) are effective alternatives to heat-activated 30% H2O2. However, interest has been expressed in the assessment of pathological effects of long-term exposure to bleaching agents such as irritation and ulceration of the gingival or other soft tissues. The aim of the present study was to determine the effect of hydrogen peroxide on apoptosis in human gingival fibroblasts (HGF). Cytochrome c, Bcl-2, Bax, Bid and caspase-3 protein expression were detected by Western blotting. HGF cell apoptosis induced by H2O2 was both dose and time dependent. The addition of H2O2 resulted in the release of cytochrome c to the cytosol, and an increase of Caspase-3 cleavage. Data suggest that oxidative stressinduced apoptosis in HGF is intrinsic pathway involved the release of apoptotic signal from mitochondria.
... Hydrogen and carbamide peroxide are unequivocally effective tooth bleaching agents that readily penetrate into the tooth structure to interact with chromogens and break them down to lighten the tooth color [2]. Despite their proven effectiveness and minimal side effects, there have been concerns about the use of highly concentrated hydrogen peroxide materials and their potential to induce intense inflammation in the pulp tissue [3][4][5]. Thus, the search for new bleaching agents that may also exhibit additional oral health care benefits continues as the oral health care professionals strive to improve oral health care products that may benefit the general public. This has prompted the need for valid and reliable methods to quickly screen for tooth bleaching efficacy evaluation in vitro, prior to undergoing rigorous clinical evaluation and processes for product approval to be marketed. ...
Article
Objectives: This study aimed to use a laboratory model to evaluate the efficacy of an experimental bleaching agent. Materials and methods: The model used human extracted molars that were treated and measured for bleaching efficacy. Teeth (n = 50) were distributed into 5 groups: Negative control (NC): immersion in water for 8 hours; Nanofibers (NFs): Experimental titanium dioxide nanofibers with stirring and light activation for 8 hours; Whitestrips (WS): Crest 3D White Glamorous White Whitestrips, 2 applications daily for 30 minutes, 14 days; 1% hydrogen peroxide (HP) standard: 1% hydrogen peroxide for 8 hours; and 30% HP standard: 30% hydrogen peroxide for 8 hours. Instrumental measurements were performed using a spectrophotometer. Results were recorded at baseline, 1-day post-bleaching, and 1-week post-bleaching. Kruskal-Wallis procedure was used to determine differences in color change. Pearson correlation was used to evaluate the relationship between visual and instrumental measurements. Tests of hypotheses were 2-sided with alpha = 0.05. Results: There was no significant difference in color parameters (L1, a1, b1, and shade guide units [SGU]) at baseline (p > 0.05). There was a significant difference among the groups for overall color change (ΔE*ab) and change in shade guide units (ΔSGU) at 1-day and 1-week post-bleaching (p < 0.05). The higher the HP concentration, the higher the color change as expressed in ΔSGU and ΔE*ab. The negative control exceeded the perceptibility threshold of ΔE* = 1.2 regardless of time point. NFs showed a decrease in chroma, but were not statistically different compared to the negative control. Conclusions: The laboratory model was successful in screening an experimental bleaching agent.
... Hydrogen and carbamide peroxides have long been used safely in oral health products and are accepted by the FDA (U.S. Food and Drug Administration). However, recently people have begun to doubt the safety of teeth whiteners such as H 2 O 2 and CP (Li 1996) because of the possibility of carcinogenic effects (Munro et al. 2006). CP causes ulcers in rats, possible attributed to Carbopol, which could increase the PC tissue adherence and retard oxygen release (Dahl and Becher 1995) and which is commonly used in the bleaching agent preparation. ...
Article
Full-text available
A rapid and effective method for carbamide peroxide (CP) quantification in pharmaceuticals is proposed. The reagentless biosensor was prepared by using lyophilized turnip extract as horseradish peroxidase (HRP) enzyme source. The biosensor presented the best performance. The measurements were carried out in 0.1 mol L-1 Pipes buffer (pH 6.0). At -100 mV vs. Ag|AgCl, a linear response range from 3.0 to 25.0 mmol L-1 was obtained. The quantification and detection limits were 1.2 and 0.4 mmol L-1, respectively, and the response time was 0.5 s. The biosensor repeatability, storage, and lifetime were excellent, allowing a satisfactory CP quantification in real pharmaceutical samples, when compared with those obtained by the official method.
... Other dental materials such as the alloys used in prostheses, restorations and orthodontic devices, composite resins, bleaching agents and glass ionomer cements have also been associated with cytotoxic effects. [31][32][33][34][35][36] The results obtained in this study do not preclude the use of acrylic resins incorporated with AgVO 3, as friable mucosa is generally more resistant to toxic substances than a cell culture because of the presence of mucin and the keratin layer. In addition, as reported earlier, bacterial toxicity results in cell toxicity in most patients. ...
Article
Objectives: This study evaluated the release of ions and the cytotoxicity of acrylic resins incorporated with silver vanadate decorated with silver nanoparticles (AgVO3 ). Background: The inhibition of the accumulation of microorganisms on the resins is critical in preventing diseases. However, the hypothesis is that the release of ions from the incorporation of AgVO3 may be important in biocompatibility. Materials and methods: Specimens of autopolymerising (AP) and heat-polymerising resin (HP) with AgVO3 were prepared and immersed in culture medium. The release of silver ions (Ag) and vanadium (V) was evaluated by mass spectrometry with inductively coupled plasma (ICP-MS) (n=9) and the cell viability of fibroblasts L929 by MTT (3-[4,5-dimethylthiazol- 2yl]-2,5-diphenyltetrazolium bromide) (n=12). The results were evaluated with analysis of variance (ANOVA), Tukey and Pearson correlation test (α=.05). Results: The groups containing AgVO3 presented a difference in relation to the control (0%) regarding the release of Ag and V (P<.0001). All groups showed a reduction in L929 viability when compared with the cellular control (100%) (P<.0001). In comparison with the control resins for HP, a reduction in the metabolism of cells occurred starting at 2.5% and for AP at 5% (P<.0001). A positive correlation was found between the concentration of AgVO3 and the ion release, and a negative between the ion release and the cell viability. Conclusions: Significant numbers of Ag and V ions were released from resins with higher concentrations of AgVO3 , presenting cytotoxicity for cells, suggesting that the use of low concentrations is indicated to avoid risks to patients.
... Dental sensitivity during and after bleaching has been associated with microscopic surface defects and enamel pores that allow rapid entry of the bleaching agent into the pulp, resulting in sensitivity [6][7][8]. Hydrogen peroxide has irritant and cytotoxic potential [9][10][11]. Clinical studies have reported a higher prevalence of gingival irritation in patients who used bleaching materials with higher concentrations of peroxide [1,12]. ...
Article
Full-text available
Objective The study evaluated the longevity, effectiveness, safety, and impact on the oral health-related quality of life of in-office dental bleaching using low-concentration hydrogen peroxides. Materials and methods Randomized, parallel, and double-blinded clinical trial was performed with 54 participants using 6% or 15% hydrogen peroxide (HP) in-office bleaching activated via hybrid LED/laser light. Tooth color was evaluated at baseline (T1), 1 week of bleaching (T2), 2 weeks of bleaching (T3) and 1 week (T4) and 6 months (T5) after finishing the bleaching using the Classical Vita™ scale and spectrophotometer. Tooth sensitivity and gingival irritation were measured with Visual Numeric Scale and Modified Gingival Index. The impact on quality of life was evaluated using the Oral Impact on Daily Performance. The data were analyzed using the Friedman, Mann-Whitney, and McNemar tests (p < 0.05). Results The group HP15% presented significant color change (ΔE) from T1 to T4 (p = 0.002) and T1 to T5 (p < 0.001). Parameters L, a*, and b* differed significantly at T3, T4, and T5 compared T1 for both groups. At 6-month follow-up, 57.1% of HP6 and 43.7% of HP15% participants migrated from B1 to a darker color. No significant differences were observed between the groups in tooth sensitivity, gingival irritation, or impact on quality of life. Conclusions Both agents showed bleaching effectiveness, but HP15% presented greater color stability than HP6%, at 6-month follow-up. The agents showed low levels of tooth sensitivity, gingival irritation, and did not affect the oral health-related quality of life of the participants. Clinical relevance Despite the greater presence of sensitivity during treatment compared with 6% hydrogen peroxide, 15% hydrogen peroxide demonstrated better bleaching effectiveness, and greater color stability at the end of bleaching and at 6-month follow-up. The use of 15% hydrogen peroxide presents more suitable results.
... 17 Munro et al. evaluated in a literature review bleaching products containing hydrogen peroxide or carbamide peroxide, related to the potential risk of oral cancer. 18 Clinical data on tooth bleaching containing hydrogen peroxide only showed evidence of mild and transient gingival irritation and tooth sensitivity, with no evidence of development of preneoplastic or neoplastic oral lesions. Exposures to hydrogen peroxide, including areas commonly associated with oral cancer, were extremely low and did not show a representative risk of promoting cell-initiation or inducing carcinogenic effects synergistically with cigarette smoke or alcohol. ...
Article
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Objetivo: realizar uma revisão integrativa da literatura sobre a indicação do clareamento dental em pacientes fumantes, com o uso de peróxidos como agente clareador, em relação à segurança do tratamento, a efetividade, a sensibilidade dentária, seu efeito na estrutura dental e a longevidade do tratamento. Por fim, o efeito de cremes dentais clareadores em pacientes fumantes foi buscado. Material e Método: foram realizadas buscas nas bases de dados PubMed, LILACS e Scopus, utilizando as palavras-chave em associação: (Bleaching OR whitening or dental bleaching) AND (smoke OR smoker OR cigarrete), em inglês e português. Os critérios de inclusão foram: artigos publicados entre 2008-2018, estudos in vitro, clínicos e revisão de literatura. Resultados: 56 artigos foram encontrados. Após análise por título, 20 artigos foram selecionados. Após leitura dos resumos, 6 artigos foram excluídos. 14 artigos foram lidos na íntegra, 6 foram excluídos de acordo com os critérios de inclusão/ exclusão e 08 artigos foram abordados nessa revisão. Conclusão: O clareamento com peróxido de carbamida 10% parece ser um método seguro em pacientes fumantes. Os peróxidos em diferentes concentrações foram efetivos no clareamento. Não houve diferença significativa entre fumantes e não fumantes em relação a sensibilidade. Os agentes clareadores não causam alterações permanentes na estrutura dentária. Em relação a longevidade, em um ano houve regressão da cor em fumantes e não fumantes e a profilaxia foi eficiente na remoção de manchas extrínsecas em pacientes fumantes, conseguindo estabilizar a cor obtida no clareamento. Os cremes dentais clareadores não foram eficazes na remoção das manchas.
... All bleaching procedures are time and concentration dependent, with wide variations in concentrations and exposure times being employed depending on dentist and patient preferences. Vital tooth-whitening procedures with hydrogen peroxide are considered safe when used as instructed ( Munro et al. 2006). Side effects and risks include increased tooth sensitivity and gingival irritation (Carey 2014). ...
Article
One of the main goals of dental treatment is to mimic teeth and design smiles in a most natural and aesthetic manner, based on the individual and specific needs of the patient. Possibilities to reach that goal have significantly improved over the last decade through new and specific treatment modalities, steadily enhanced and more aesthetic dental materials, and novel techniques and technologies. This article gives an overview of the evolution of aesthetic dentistry over the past 100 y from a historical point of view and highlights advances in the development of dental research and clinical interventions that have contributed the science and art of aesthetic dentistry. Among the most noteworthy advancements over the past decade are the establishment of universal aesthetic rules and guidelines based on the assessment of natural aesthetic parameters, anatomy, and physiognomy; the development of tooth whitening and advanced restorative as well as prosthetic materials and techniques, supported by the pioneering discovery of dental adhesion; the significant progress in orthodontics and periodontal as well as oral and maxillofacial surgery; and, most recently, the implementation of digital technologies in the 3-dimensional planning and realization of truly natural, individual, and aesthetic smiles. In the future, artificial intelligence and machine learning will likely lead to automation of aesthetic evaluation, smile design, and treatment-planning processes.
... At concentrations of 10% hydrogen peroxide or higher, the chemical was found to be potentially corrosive to mucous membranes or skin and can cause a burning sensation and tissue damage [15][16][17]. Because of the hydrogen peroxide potential to interact with DNA, concerns with carcinogenicity and cocarcinogenicity of hydrogen peroxide have been raised, although these concerns so far have not been substantiated through research [5,6,18,19]. With an aim to provide safe and efficient reduction of extrinsic stains at home and teeth whitening, and without changing the daily dental hygiene routine, Home Skinovations LTD. ...
... Given this opinion, a comprehensive review was undertaken of the available safety data on various tooth whitening products, and hydrogen peroxide in particular, to assess the carcinogenic risks posed to humans by hydrogen peroxide exposures from the use, both intended and exaggerated, of tooth whitening products. 3 This article presents a summary of this review regarding the safety of tooth whitening products with respect to their potential carcinogenicity in humans. ...
Article
Tooth whitening products containing hydrogen peroxide or carbamide peroxide were evaluated in this review for potential oral cancer risk from their use. Hydrogen peroxide is genotoxic in vitro, but not in vivo. Hydrogen peroxide was not considered to pose a genotoxic risk to humans. The animal toxicology data relevant to the assessment of the carcinogenicity of hydrogen peroxide do not indicate that it has significant carcinogenic activity at any site, including the oral cavity. Hydrogen peroxide was found to enhance the carcinogenic effects of potent DNA reactive carcinogens in experimental animals. However, these experimental conditions are artificial as they are related to high exposures and are of no relevance to potential human exposures to low quantities of hydrogen peroxide from the use of tooth whitening products. Clinical data on hydrogen peroxide-containing tooth whitening products show no evidence for the development of preneoplastic or neoplastic oral lesions. Exposures to hydrogen peroxide received by the oral cavity are exceedingly low, of short duration (30–60 minutes), and could not plausibly enhance any carcinogenic risk associated with exposure of the oral cavity to chemicals in cigarette smoke or to alcohol, both known risk factors for the development of oral cancer. Based on a comprehensive review of the available literature and research, the use of tooth whitening products containing hydrogen peroxide or carbamide peroxide does not appear to pose an increased risk of oral cancer in the general population, including those persons who are alcohol abusers and/or heavy cigarette smokers.
Article
(1) To assess the knowledge of a group of experts in head and neck cancer regarding risk factors for oral cancer; (2) to describe the quality of the available literature on the topic of oral cancer risk factors; and (3) to compare expert opinion about oral cancer risk factors with the literature. Survey of head and neck cancer experts and extensive literature review and classification of levels of evidence for published data. Extensive data demonstrating the level of published literature support for or against many compounds and behaviours are presented. In several cases, there was good correlation between expert opinions and literature support, whereas for others, there was a clear discordance. Experts in oral cancer are in agreement that tobacco smoking and betel use are significant risk factors for the development of oral cavity carcinoma. There is a lack of agreement about the risks of alcohol, poor-fitting dentures, maté tea, and a diet low in fruits and vegetables. Sufficient data have been published demonstrating the risk associated with each factor; however, it appears that the most current data and research are not as available to medical professionals as they should be. The perceived risks of tobacco chewing and use of khat were not substantiated by a solid foundation of data. A higher degree of concordance among experts was found for riskier health habits such as tobacco, alcohol, and betel chewing, whereas the votes were more dispersed for the risk factors that received lower ratings.
Article
Objectives: To provide dentists and dental hygienists a deep description of vital and non vital teeth chair side bleaching active agents and procedures, with a special attention to indications and contraindications at the treatment, to realize a success aesthetic procedure. Materials and methods: Author's personal and professional experience on a patient's high number with different commercial brands and technology instruments for power bleaching is described. The most recent literature on the subject is also examined. Results and conclusions: Active bleaching agents and power bleaching procedures of vital and non vital teeth have been carefully deepened with a special attention to indications and contraindications at the treatment and informed consent. Power bleaching is a treatment required by patient who needs an immediate result. Therefore there is a strong need to promote an operators' high professional knowledge.
Article
The distinction between carcinogens with DNA-reactive and epigenetic modes of action and the application of mode-of-action considerations to risk assessment is reviewed. A bioindicator-based risk assessment strategy is described. This approach involves the use of mechanistic data to establish a “toxicologically insignificant daily intake”.
Article
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Objective This experimental study aimed to observe the effects of a tooth whitening product, whose active agent is 6% hydrogen peroxide, on the gastric mucosa of healthy and non-tumour gastric pathology animals. Material and Methods Fifty Wistar-Han rats were used and then distributed into 5 groups, one for control and four test groups in which the bleaching product was administered in animals with and without non-tumour gastric pathology (induced by the administration of 1 sample of 50% ethanol and 5% of drinking water during 6 days) at different times of study by gavage. There was a decrease in body weight in animals of groups handled during the study period, which was most pronounced in IV and VA groups. Changes in spleen weight relative to body weight revealed no statistically significant changes. An analysis of the frequency was performed on the results of macroscopic observation of the gastric mucosa. Results The gastric mucosa revealed lesions in all manipulated groups, being more frequent in groups III and IV. It appears that there is a synergism when using hydrogen peroxide and 50% ethanol in the same group. Conclusion Therefore, it seems that there are some signs of toxicity 3 to 4 days after administration of 6% hydrogen peroxide. The prescription of these therapies must be controlled by the clinician and the risks must be minimized.
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Patients seeking the expertise of facial plastic surgeons for facial aesthetic improvement may also desire or benefit from dental aesthetic procedures. This paper reviews current treatment options available in cosmetic dentistry. Many techniques exist to improve dental aesthetics in color, position, shape, size, alignment and overall smile appearance. Although orthodontic therapy is still an important modality for smile aesthetics, some simpler procedures can provide acceptable aesthetic results. Comparison of external dental bleaching techniques reveals similar long-term results for in-office and at-home bleaching; in-office treatments, however, may provide the benefit of faster results. Internal dental bleaching is an effective method for correcting nonvital teeth coloration. Enamel shaping via either direct tooth contouring or the application of resins or veneers to tooth surfaces can correct defects, asymmetries and shape or rotation problems. Veneers or crowns are also options to correct intrinsic dental stains not amenable to bleaching techniques. Treatments to refine gingival margins and borders are another proven beneficial cosmetic procedure. A myriad of techniques exist to correct a patient's particular concerns. Correction of discoloration is usually feasible as is the improvement of a patient's smile and overall dental aesthetics.
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A case-control study of oral and pharyngeal cancer conducted in four areas of the United States provided information on the tobacco and alcohol use of 1114 patients and 1268 population-based controls. Because of the large study size, it could be shown that the risks of these cancers among nondrinkers increased with amount smoked, and conversely that the risks among nonsmokers increased with the level of alcohol intake. Among consumers of both products, risks of oropharyngeal cancer tended to combine more in a multiplicative than additive fashion and were increased more than 35-fold among those who consumed two or more packs of cigarettes and more than four alcoholic drinks/day. Cigarette, cigar, and pipe smoking were separately implicated, although it was shown for the first time that risk was not as high among male lifelong filter cigarette smokers. Cessation of smoking was associated with a sharply reduced risk of this cancer, with no excess detected among those having quit for 10 or more years, suggesting that smoking affects primarily a late stage in the process of oropharyngeal carcinogenesis. The risks varied by type of alcoholic beverage, being higher among those consuming hard liquor or beer than wine. The relative risk patterns were generally similar among whites and blacks, and among males and females, and showed little difference when oral and pharyngeal cancers were analyzed separately. From calculations of attributable risk, we estimate that tobacco smoking and alcohol drinking combine to account for approximately three-fourths of all oral and pharyngeal cancers in the United States.
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The objective of this study was to determine the effects of hydrogen peroxide alone and in combination with 7,12-dimethylbenza[a]anthracene &lpar;DMBA&rpar; in the oral cavity because H2o2, has been implicated as a complete carcinogen or cocarcinogen in two animal models. In the two independent studies, golden Syrian hamsters were used to evaluate the carcinogenic and cocarcinogenic potential of dentifrices containing H2o2 and NaHCO3. In the first study, the cocarcinogenic potential of a dentifrice containing 0.75&percnt; H2O2&sol; 5&percnt; baking soda was compared with that of a commercial dentifrice with similar ingredients except baking soda and H2O2. In the second study, the cocarcinogenic potential of a dentifrice formulated with 1.5&percnt; H, sb>2O2&sol;7.5&percnt; baking soda was compared with a mixture of 3&percnt; H2O2&sol;baking soda. All materials were applied to the right cheek pouches of experimental animals, and the left cheek pouches were untreated. In the first study. 0.5&percnt; DMBA was administered five times weekly for 20 weeks, and the dentifrices were applied immediately after the DMBA. Dentifrices or mineral oil alone were also applied five times weekly. In the second study. 0.5&percnt; DMBA or 0.25&percnt; DMBA were applied three times weekly for 16 weeks; dentifrices &lpar;or 3&percnt; H2O2&sol;baking soda&rpar; were applied five times weekly for 16 weeks. The dual-phase dentifrice containing 0.75&percnt; H2O2&sol;5&percnt; baking soda was not carcinogenic, and in combination with DMBA resulted in no observable acceleration of tumor onset, compared with DMBA alone. In fact, animals treated with 0.5&percnt; DMBA and the H2O2&sol;baking soda dentifrice had a significantly delayed onset of tumor formation than did animals treated with DMBA alone. In the second bioassay, an increased latency period for tumor formation was observed with 0.5&percnt; DMBA and a dual-phase dentifrice containing 1.5&percnt; H2O2&sol;7.5&percnt; baking soda, compared with 0.5&percnt; DMBA alone. With 0.25&percnt; DMBA, latency was not affected by addition of the dual-phase dentifrice. In contrast, animals receiving 0.25&percnt; DMBA and 3&percnt; H2O2&sol; NaHCO3 had a significantly lower rate of tumor formation and overall mass incidence. Croton oil also reduced the rate of tumor formation when applied with 0.25&percnt; DMBA. Histopathologic examination of cheek pouches revealed squamous cell carcinomas in the majority of DMBA-treated animals. Cheek pouches of DMBA-treated animals killed at interim times indicated a progression from keratotic changes and&sol;or dyskeratosis at 6 weeks with the occurrence of carcinomas in approximately half the animals examined at 12 weeks. No significant histopathologic abnormalities were observed in animals not receiving DMB A other than slight keratosis in the oral mucosa of one or two animals per group. These results demonstrated that an oral product containing baking soda and hydrogen peroxide was not carcinogenic, and that baking soda and H2O2 did not enhance the tumorigenicity of DMB A. Furthermore, the tumor-igenic response of DMBA was reduced by coadministration of 3&percnt; H2O2 and sodium bicarbonate.
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Exposure of Dulbecco's modified Eagle's tissue culture medium to visible fluorescent light generated photoproducts toxic to human cells in culture. Toxicity manifested at the chromosome level was increased chromosome aberrations and sister chromatid exchanges in cells exposed to the photoproducts. Hydrogen peroxide (H2O2), a major photoproduct, induced SCE but failed to increase chromosome aberrations. Pure H2O2, or the H2O2 generated in light-exposed medium, was necessary and sufficient for inducing all the increase in SCE. However, H2O2 was necessary but insufficient to cause most of the chromosome aberrations. Only when acting synergistically with other photoproducts did H2O, induce extensive chromosome aberrations. The relatively high cell densities at near confluence levels used in these experiments were less sensitive to light-induced effects, nevertheless the entire light exposure dosage range effected photoproduct production adequate for inducing SCE and chromosome aberrations. Thus, mammalian tissue and cell culture media can receive sufficient dosage from fluorescent lights illuminating rooms and culture hoods for generation of photoproducts causing gross and insidious SCE and chromosome alterations.
In bioassays conducted under controlled, comparable conditions, weak direct mutagenicity responses were observed for hydrogen peroxide in the standard (Ames test) agar plate incorporation bioassay with Salmonella typhimurium strains TA97, TA98, TA102, and TA1537, in a 20 min preincubation test with strains TA97, TA98, TA100, TA102, TA1537, and TA1538, and in a liquid incubation modification using strain TA1537. These results conclusively demonstrate that hydrogen peroxide is a weak mutagen, especially in strains that are sensitive to oxidative damage under suitable bioassay conditions.
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Background: The aims of this study were to identify differences in oral cancer incidence and mortality between sexes, age groups, oral sites and Australian States and Territories and recent trends in oral cancer incidence, mortality and age-profile over time. Methods: Data were obtained from the Australian Institute for Health and Welfare and were age-standardized to the Australian 1991 Population Standard. Differences and trends were assessed with the Wilcoxon matched-pairs signed-ranks test and the Spearman correlation test, respectively. Results: In Australia in 1996, there were 2173 new oral cancers and 400 deaths due to oral cancer, the majority of oral cancers were in the 60+ age group, oral cancer affected men more than women (>2:1), lip cancer accounted for more than 50 per cent of oral cancers and the oral cancer mortality-to-incidence (M:I) ratio was greatest in ACT and NSW and least in QLD and SA. From 1983 to 1996, the annual incidence of lip cancer increased while the M:I ratio of lip cancer decreased. The annual incidence of cervical cancer decreased whereas the annual incidence of intra-oral cancer remained constant. The M:I ratio of cervical cancer was consistently lower than the M:I ratio of intra-oral cancer. Conclusions: Reducing exposure to environmental carcinogens, increasing public awareness and population screening may reduce the incidence and mortality of oral cancer in Australia.
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Chromosomal aberrations were observed in cultured mammalian cells (CHO-K1 Chinese hamster cells, V79 Chinese hamster cells, Syrian hamster cells, and BALB/c mouse cells) after treatment with hydrogen peroxide (H2O2; 0.1-0.5mM or 0.01-0.1mM) for 3h. The cytotoxic and clastogenic effects of H2O2 were clearly reduced by the addition of catalase. In contrast to the clastogenic potential, H2O2 did not enhance the frequency of mutation in V79 cells, whether the marker for mutation was 8-azaguanine resistance or ouabain resistance.
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Independent carcinogenic effects of alcohol drinking and tobacco smoking as well as their interaction can be usefully studied in a population of heavy drinkers and smokers. A hospital-based case-control study was conducted during 1972 to 1983 in a large Veterans hospital in East Orange, New Jersey. A total of 359 oral cavity-oropharynx cancer cases and 2280 controls were interviewed according to tobacco smoking, use of smokeless tobacco, alcoholic beverage, coffee and tea drinking, race, family origin, religion, and occupation as bartender. Odds ratio of oral cancer increased up to the level of 35 cigarettes per day and 21 whiskey equivalents per day: no further increase was found for higher level of exposure to either factor. A protective effect of quitting smoking was found, but the number of former smokers was small. No difference occurred in oral cancer risk according to type of alcoholic beverage drunk. An interaction effect compatible with a multiplicative model was found between the two exposures. Blacks were at lower risk than whites, and, in the latter group, individuals of Italian origin were at lower risk than individuals from northern or central European countries. Alcohol drinking and tobacco smoking were responsible for the majority of oral cancer cases in this population of US Veterans.
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Purpose: The purposes of this retrospective case series study were to evaluate safety issues and determine participants' perceptions of a nightguard vital bleaching (NGVB) technique approximately 10 years post-treatment (average, 118 mo; range, 108–144 mo). Materials and Methods: The study sample included 30 (79%) of 38 participants who had completed a previous NGVB study using a 10% carbamide peroxide solution (Proxigel® or Gly-Oxide®) in a custom tray for 6 weeks. Participants were asked whether there had been any change in the shade of their teeth post-treatment and, if so, to quantify the change on a verbal scale. In addition, 19 participants had gingival index and tooth vitality evaluated clinically, external cervical root anatomy evaluated radiographically, and enamel surface changes evaluated microscopically. Results: Thirty-five (92%) of the original 38 participants had successful lightening of their teeth. At approximately 10 years post-treatment (average, 118 mo; range, 108–144 mo), external cervical resorption was not diagnosed and gingival index and tooth vitality findings were considered within the normal expectations for the sample studied, suggesting minimal clinical post-NGVB side effects at approximately 10 years. Scanning electron microscopic observations did not reveal substantial differences between treated and nontreated surfaces. Color stability, as perceived by 43% of the participants, may last approximately 10 years (average, 118 mo; range, 108–144 mo) post-treatment.
Article
Purpose: The purpose of this longitudinal whitening study was to determine the stability, post-treatment side effects, and patient satisfaction after 6 months of active treatment of tetracycline-stained teeth with 10% carbamide peroxide at 0 and 54 months post treatment.Materials and Methods: Twelve patients who completed the study (80%) were contacted and asked to participate in a survey concerning their whitening experience. Subjects were asked whether there had been any change in the shade of their teeth after treatment, and if they had experienced any side effects that they believed were treatment-related. Eight of the twelve patients underwent clinical examination.Results: Ten patients (83%) reported no obvious shade change or only a slight darkening not noticed by others. Two (17%) reported a slight darkening that is probably noticeable by other people, but no one reported moderate darkening or significant darkening back to original shade. All respondents (n = 12) denied having to have a crown or root canal that they believed was treatment-related. Examiners who compared preoperative and post-treatment photographs and Vita shade values were in agreement with the patients' perceptions of shade change. The degree of improvement was significant for both the immediate (0 mo) and the 54-month post-treatment comparison with the pretreatment shade (p < .005 and p < .01 respectively).
Article
Background: The role of tobacco and alcohol consumption and the frequency of intake of a selected number of indicator foods as causes of cancer were investigated in a case-control study conducted in northern Italy. Methods: One hundred two men with cancer of the tongue, 104 patients with cancer of the mouth, and 726 control subjects (the latter admitted to the hospital for acute nonneoplastic disease without respiratory illness) were interviewed. Results: Similarly strong associations were observed with cigarette smoking (odds ratio [OR], 10.5 and 11.8 for current smokers versus never smokers in cancer of the tongue and mouth, respectively) and alcohol (OR, 3.4 and 3.0 for > or = 60 versus < or = 19 drinks/week). The risk conferred by pipe or cigar smoking, although based on only 12 smokers who did not smoke cigarettes, seemed, however, to be lower for cancer of the tongue (OR, 3.4) than cancer of the mouth (OR, 21.9). Selected indicator foods and beverages, including green vegetables, carrots, fresh fruits, whole-grain bread and pasta, coffee, and tea also affected the cancer risk similarly in the two sites. The beneficial influence of such foods and beverages seemed, however, to be more marked for cancer of the mouth than for cancer of the tongue. Conclusions: This study suggested that, although none of the differences in the effects between cancer sites was statistically significant, tobacco from pipes and cigars and the cleansing effect of some foods of plant origin and nonalcoholic beverages may influence the risk of cancer of the tongue less strongly than the risk of cancer of the mouth.
Article
Purpose: The purpose of this longitudinal whitening study was to determine the stability, post-treatment side effects, and patient satisfaction at 90 months post treatment after 6 months of active treatment of tetracycline-stained teeth with 10% carbamide peroxide. Materials and Methods: Fifteen of 21 participants enrolled in the study (71%) were contacted and asked to participate in a survey concerning their whitening experience. Participants were asked whether there had been any change in the shade of their teeth after treatment and if they had experienced any side effects that they believed were treatment related. Eight of the 15 participated in a clinical examination. Results: Nine participants (60%) reported no obvious shade change or only a slight darkening not noticed by others. None reported darkening back to the original shade; however, four had re-treated their teeth. Examiners were in agreement with the participants' perception of shade change upon comparing pretreatment and post-treatment photographs and Vita® shade (Vita Zahnfabrik D-79713, Bad Sackingen, Germany) values. The degree of improvement over the pretreatment shade was significant for the 90-month post-treatment shade (p < .01). All respondents (n = 15) denied having to have a crown or root canal or tooth sensitivity that they believed was treatment related. CLINICAL SIGNIFICANCE The results of this study of nightguard vital bleaching indicate that tetracycline-stained teeth can be whitened successfully using extended treatment time and that shade stability may last at least 90 months post treatment (range 84–100 mo). Patients participating in this study were over-whelmingly positive about the procedure in terms of shade retention and lack of post-treatment side effects.
Article
Reducing agents and cysteine, cysteamine, glutathione, ascorbic acid and H2O2 with and without the addition of Cu2+ did not increase significantly the frequency of mutations in the Salmonella test at non-toxic concentrations but triggered a marked DNA repair synthesis and induced a relatively high frequency of chromosome aberrations in cultured mammalian cells. Both latter effects were reduced by the addition of catalase to solutions of the reducing agents plus Cu2+. To avoid 'False Negatives' in mutagenicity screening the use of several test subjects including mammalian cells seems to be required.
Article
Reciprocal exchanges of DNA in sister chromatids (SCEs) are induced by various carcinogens and mutagens, although the quantitative relationship between the number of mutations and SCEs induced varies among chemicals. Nevertheless, the analysis of SCE production by various agents is often proposed as a sensitive and quantitative assay for genetic damage of the sort leading to mutation and cancer. In V-79 Chinese hamster cells we have been measuring DNA damage by alkaline elution, mutation induction as detected by 6-thioguanine resistance, and cytotoxicity as detected by colony formation for different physical and chemical agents. Some of the agents produced varying forms of DNA damage but undetectable increases in either mutation or toxicity. We report here that some undetectably mutagenic and/or toxic agents produce increases in SCE frequency and that DNA single-stranded breaks, DNA--DNA interstrand cross-links, and DNA--protein cross-links are not necessary for SCE.
Article
Cysteine, cysteamine and glutathione all induce sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells when applied to cell cultures at concentrations between 10−4 and 10−2 M. Acute exposure of cells to thiol compound for a period of 2–3 h resulted in a unique dose-response relationship in each instance. This consisted of two peak SCE frequencies, one at either extreme of the concentration range. Each peak corresponded to a 2–3-fold increase over the spontaneous level. A chronic exposure of 24 h, in contrast, resulted in a dose—response relationship consisting of a single peak SCE frequency (representing a 4–5-fold increase over the spontaneous level) at a concentration of approx. 4 × 10−4 M. The effect of Cu2+ ions included in the medium at a concentration of 10−5 M was to increase the toxicity and, at some concentrations, the SCE levels occurring after either acute or chronic exposure to thiols.
Article
Peracetic acid was a potent tumor promoter and a weak complete carcinogen on the skin of female ICR Swiss mice. "Decomposed peracetic acid" was inactive as a tumor promoter, as were 3% [hydrogen peroxide and 5%] urea peroxide; 1% perbenzoic acid and m-chloroperbenzoic acid were active tumor prototers.
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Knowledge about premalignant lesions in the mouth is exceedingly limited. Their incidence is unknown since, unlike cancer, they are not registered, and in any case it would be exceedingly difficult to lay down criteria for registration purposes. Such data as are available refer almost entirely to persistent white lesions which are given the purely clinical description of leukoplakia. Nevertheless this is not to say that premalignant lesions are always white, or that persistent white lesions are always premalignant. Premalignant change can be diagnosed only at a histological level and depends on the recognition and evaluation of epithelial changes. Though criteria for recognition of the various components of epithelial atypia have been described, the final assessment is essentially subjective. Other interesting and potentially valuable investigative methods have been described, which aim to minimize the subjective element by identifying and quantifying parameters of predictive value. So far, however, these remain research methods. There is also a paucity of material for investigation, in that oral cancer accounts for only 1% of malignant neoplasms, and in the whole of England and Wales the average (1962-67) number of registered cases of oral cancer is less than 1200 annually. Of this relatively small number, few have been detected before frank carcinomatous change has developed, and in fact there are no data whatsoever on the number of carcinomas that pass through a detectable premalignant state. Very little information exists on the natural history of dysplastic epithelial lesions, tracing the progress or regression of atypia by means of sequential biopsies. In any case criticism can be levelled even against any such series of sequential biopsies in that either a biopsy samples only part of the lesion, in which case it provides no information about the remainder, or alternatively the whole lesion may have been excised, in which case its natural development is likely to have been aborted. In considering the problems of evaluation, an analogy can be drawn between premalignant oral lesions and preinvasive lesions of the uterine cervix. As to premalignant lesions of the mouth, assessment is more difficult because cellular changes are less severe, and there is much less information than is available for the uterine cervix. In addition there is no certainty as to the most effective form of treatment.
Article
The site and size of 222 asymptomatic, primarily erythroplastic, cancers of the oral mucosa in 161 patients have been prospectively documented. Of 207 intraoral lesions (excluding 15 of the lip), 201 (97.1%) were found in three locations; floor of the mouth (101), ventral or lateral tongue (36), and soft palate complex (64). Of the 101 in the floor of the mouth, 73 occurred in the anterior portion with 33 involving the papilla at exit of Wharton's Duct (submaxillary gland). Of the cancers 84.2% were 2 cm or less and 41.9% were 1 cm or less. Of the lesions 2 cm or less 70.6% were invasive carcinoma. Minimal size does not preclude invasiveness. In view of the apparent predilection of oral carcinoma for particular sites (where there is no obvious agent), rather than random occurrence, the three aforementioned sites are designated as high risk areas which deserve particular scrutiny in an examination of the oral cavity. It is incumbent upon the clinician to biopsy all asymptomatic, persisten (14 days or more) mucosal aberrations in the high risk areas, especially those with erythroplastic components, regardless of size.
Article
A single 7,8-dihydro-8-oxoguanine (G8-oxo; 8-hydroxy-guanine) adduct in the lacZα gene of bacteriophage M13 DNA induces a targeted G—T transversion after replication in Escherichia coli (Biochemistry, 29, 7024–7031 (1990)). This mutation is thought to be due to the facile formation during DNA synthesis of a Q8-oxo.base pair, where G8-OXO is in the syn conformation about the deoxyglycosyl bond. A related modified purine, 7,8-dihydro-8-oxoadenine (Asup8-oxo; 8-hydroxy-adenine), is an abundant product found in irradiated and oxidized DNAs. Similar to G8-oxo as a mono-nucleoside A 8-0xO assumes the syn conformation. This work has assessed the relative mutagenicities of A8-oxo and G8-OXO ;n the same experimental system. A deoxypentanucleotide containing A8OXO [d(GCT-A8-0X0G)] was synthesized. After 5′-phosphorylation with [γ-32P] ATP, the oligomer was ligated into a duplex M13mp19-derived genome at a unique Nhel restriction site. Genomes containing either A8-OxO (at position 6275, [+] strand) or G8-oxo(position 6276) were denatured with heat and introduced into E.coli DL7 cells. Analysis of phage DNA from mutant plaques obtained by plating immediately after transformation (infective centers assay) revealed that G8-oxo induced G—T transversions at an apparent frequency of ˜0.3. The frequency and spectrum of mutations observed in DNA sequences derived from 172 mutant plaques arising from the A-8oxo-modified DNA were almost indistinguishable from those generated from transfection of an adenine-containing control genome. We conclude that A8-oxo is at least an order of magnitude less mutagenic than G8-0x0 in E.coli cells with normal DNA repair capabilities.
Article
We carried out two case-control studies on the relative risk of head and neck cancer in association with tobacco and alcohol consumption. The first study carried out at the ENT Department of the University hospitals of Heidelberg and Giessen (FRG) comprised 200 male patients with squamous cell cancer of the head and neck and 800 control subjects matched for sex, age, and residential area (1:4 matching design). Of the tumour patients, 4.5% had never smoked, in contrast to 29.5% of the control group. The average tobacco and alcohol consumption of the patients was approximately twice as high as in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer. Tobacco and alcohol increased the risk of head and neck cancer in a dose-dependent fashion and acted as independent risk factors. In heavy smokers (greater than 60 pack-years) a relative risk of 23.4 (alcohol adjusted) was calculated. Combined alcohol and tobacco consumption showed a synergistic effect. The risk ratio increased more in a multiplicative than in an additive manner. Oral and laryngeal cancer were associated with the highest tobacco-associated risk values. The highest ethanol-associated risk values were associated with oropharyngeal and laryngeal cancer. The second study was carried out at the ENT Department of the University of Heidelberg on 164 males with squamous cell carcinoma of the larynx and 656 control subjects matched for sex, age and residential area (1:4 matching design). Of the cases, 4.2% had never smoked, compared with 28.5% of the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The conservative technique for bleaching vital teeth using a nightguard and a 10% carbamide peroxide solution has captured the esthetic interests of the dental profession. The purpose of this article is to assess the safety of the products used in this bleaching technique based on results from past related research and current research. Ten percent carbamide peroxide solutions used in numerous studies have demonstrated tissue-healing properties as well as a propensity for the reduction of plaque and gingivitis. None of these clinical studies revealed any untoward or detrimental side effects, and all demonstrated beneficial effects. Although some concern exists regarding the potentiating effects of peroxide solutions in the presence of known carcinogens, concerns of toxicity or damage to hard and soft tissues appear unfounded. The majority of current and past research and literature indicates that the current use of a 10% carbamide peroxide solution in the method advocated for bleaching vital teeth is apparently safe when administered properly under the supervision of a dentist.
Article
This review has focused on the importance of cellular proliferation in neoplasia induced by nongenotoxic carcinogens and has not attempted to address the mechanisms involved in the progression from the hyperplastic to the neoplastic state. Major advances in this area are likely in the next decade and should explain how cells in an abnormally high proliferative state are rendered more vulnerable either to the action of endogenous or environmental mutagens or to defects in cell reproduction, thus providing the stimulus for progression to neoplasia (165). In this review evidence has been presented to support the hypothesis that sustained tissue damage induced by nongenotoxic compounds in rodents predisposes to tumor development. The evidence has been obtained by drawing from the published findings of experimental rodent studies conducted over the past 50 years. The experience gained at various sites in the rodent including the connective tissue, liver, bladder, and forestomach shows the existence of a threshold dose for various test materials/agents, below which neither sustained tissue damage nor tumor induction occurs but above which level both effects are manifest. Taken collectively, an overall picture emerges that sustained cell proliferation renders various sites in the rodent vulnerable to tumor development. The validity of this hypothesis is of importance to the evaluation of carcinogenic risk of chemicals to humans. For those nongenotoxic carcinogens known to cause characteristically defined and sustainable tissue damage as a precursor of tumor development in rodents, it should be possible to establish a threshold dose below which both effects disappear and upon which a safety margin in humans can be based. Some limited evidence supports an association between chronic tissue injury and neoplastic development in humans. Note, however, that certain types of induced tissue damage may be rodent-specific and therefore have no relevance for humans. We conclude that the appearance of persistent tissue damage predisposes to tumor development in rodents exposed to nongenotoxic carcinogens and that systematic studies in rodents should provide a rational basis for arriving at a safety margin in humans exposed to such agents.
Article
The present investigation was undertaken to determine the types and extent of DNA damage resulting from incubation of primary cultures of bovine lens epithelial cells with hydrogen peroxide. Significant numbers of DNA single-strand breaks were detected by alkaline elution after exposure to as little as 25 microM H2O2 for 5 min at 37 degrees C. The extent of single-strand breakage was concentration dependent and linear from 25 to 200 microM H2O2. The observed single-strand breaks appear primarily due to the action of the hydroxyl radical via a Fenton reaction as both an iron chelator, 1,10-phenanthroline and OH. scavengers, including DMSO, KI and glycerol, significantly inhibited the DNA-damaging effect of H2O2. Diethyldithiocarbamate, an inhibitor of superoxide dismutase, further potentiated the DNA-damaging effects of H2O2, presumably by increasing the steady-state concentration of Fe2+. DNA-protein cross-linking was not observed. In addition, significant levels of 5,6-saturated thymine residues or pyrimidine dimers were not detected after modification of the alkaline elution methodology to allow the use of either E. coli endonuclease III or bacteriophage T4 endonuclease V, respectively. No double-strand breaks were detected after incubation of epithelial cell cultures with H2O2 concentrations of up to 400 microM for 10 min and subsequent neutral filter elution. Since, in vivo, the lens epithelium contains populations of both quiescent and dividing cells, the degree of susceptibility to oxidative damage was also studied in actively growing and plateau-phase cultures. Reduced levels of single-strand breakage were observed when plateau-phase cultures were compared to actively growing cells. In contrast, essentially no differences in repair rates were noted at equitoxic doses of H2O2. The above results suggest that lens epithelial cells may be particularly sensitive to oxidative damage and thus are a good model system in which to study the effects of oxidative stress.
Article
In 1982, Levin et al. published a paper describing a new Salmonella typhimurium strain, TA102, for detecting mutagenic agents that react preferentially with AT base pairs. This strain has an AT base pair at the critical mutation site within the hisG gene, which is located on a multicopy plasmid, pAQ1; the chromosomal copy of the hisG gene has been deleted. It also has an intact excision repair system, thus facilitating the detection of cross-linking agents, and carries the mutator plasmid, pKM101. Although TA102 has been shown to be reverted by certain mutagenic agents that are not detected in the usual battery of strains (TA1535, TA1537, TA1538, TA98 and TA100), there has been a general reluctance within the field to include TA102 as one of the standard screening strains. This may in part result from the difficulties which have been experienced in many laboratories in maintaining the strain, and in obtaining reproducible spontaneous and induced revertant counts. At Glaxo we routinely include certain Escherichia coli strains in our microbial test battery, and were aware that some of the genetic features offered by TA102 were already being covered by these strains. For example, E.coli WP2 (pKM101) has an AT base pair at the critical mutation site within the trpE gene, is excision proficient (and thus will detect cross-linking agents) and carries the pKM101 plasmid to enhance error-prone repair. From the published literature it was apparent that a number of the 'TA102 specific' mutagens could be detected in E.coli e.g. neocarzinostatin, UV and 8-MOP plus UV.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Hydrogen peroxide (H2O2) was shown to be mutagenic in a number of strains of Salmonella typhimurium. Strain SB1106p (hisC3108, hisO1242, pKM101), a newly-constructed strain carrying the histidine mutation at a UGA chain-terminating codon, was more responsive to H2O2 than TA104 or TA102, the two hisG428 strains originally developed for detecting oxidative mutagens. The largest proportional increase in revertants of strain TA104 was in the fraction of intragenic deletions. Three other strains (TA97, SB1111 and SB1106) gave unequivocal positive responses to H2O2 in both the liquid pre-incubation procedure and standard plate incorporation procedure. The response of TA100 varied among experiments, ranging from negative to a weak positive. Variations in the catalase content among the tester strains did not correlate with the relative responses obtained in the mutagenicity assays.
Article
Mutagenic 1,2-dicarbonyls have been reported to occur in coffee and other beverages and in various foods. We have measured the induction of sister-chromatid exchanges (SCEs) and endoreduplicated cells (ERCs) to determine the genotoxicity of various 1,2-dicarbonyl compounds in Chinese hamster ovary (CHO) AUXB1 cells and human peripheral lymphocytes. The 1,2-dicarbonyls glyoxal, methylglyoxal and kethoxal each induced highly significant increases in both SCEs and ERCs in AUXB1 cells. Glyoxal and kethoxal induced SCEs but not ERCs in human peripheral lymphocytes. In addition, hydrogen peroxide induced highly significant levels of SCEs and ERCs in AUXB1 cells. Bisulfite, which reacts with carbonyl groups to form addition products, significantly reduced the frequency of SCEs and the proportion of ERCs when glyoxal, methylglyoxal, kethoxal and diacetyl were administered to AUXB1 cells. In addition, bisulfite blocked the formation of ERCs, but not SCEs, induced by hydrogen peroxide. These in vitro results suggest that 1,2-dicarbonyls may play an important role in the genotoxicity of some foods and beverages.
Article
Glutathione and L-cysteine, in the presence of rat kidney post-mitochondrial supernatant (S9) fraction, and various forms of active oxygen were investigated for mutagenicity in seven his- strains of Salmonella typhimurium. Glutathione and L-cysteine showed qualitatively and quantitatively virtually identical mutagenic activities. The number of mutants induced in strain TA97 was 3-4 times higher than in TA100, the strain in which the mutagenicity was originally detected. Mutagenic effects were also observed in strains TA92, TA102 and TA104, but not in TA1535 and TA1537. Hydrogen peroxide, superoxide and glucose/glucose oxidase in the presence and absence of kidney S9 fraction showed pronounced mutagenic effects in strains TA104 and TA102. Additionally, weak mutagenic effects were observed in TA100, while the remaining strains, including TA97, were not responsive. These mutagenicity spectra suggest that the mutagenic species formed from glutathione and L-cysteine are similar, if not identical, and are different from hydrogen peroxide, superoxide and other oxygen species derived from them. Further support for this notion was given when it was observed that catalase did not affect the mutagenicity of glutathione and that superoxide dismutase showed a significant effect only when used in milligram quantities. This study shows that mutagenicity spectra may be useful in the elucidation of activation pathways. Furthermore, it is interesting to note that all the compounds and preparations showing a positive response in the Ames test in the present study occur endogenously in organisms: glutathione, L-cysteine, hydrogen peroxide, superoxide, glucose, glucose oxidase and kidney S9 fraction (which was mutagenic in several strains).
Article
Hydrogen peroxide induces lesions in cells similar to those from ionizing radiation, by a Fenton-type production of hydroxyl radicals. At 4 degrees C significant levels of DAN single-strand breaks (ssb) could be measured using the alkaline elution technique, after a 20-min incubation with 10(-5) mol dm-3 H2O2. Only at higher concentrations of H2O2 (greater than 10(-4) mol dm-3) where the levels of ssb measured corresponded to that induced by more than 18 Gy of X-rays, was any significant cell killing detected in a clonogenic assay. Cell killing was observed to coincide with the measurement of significant levels of DNA double-strand breaks (dsb) using the filter elution technique at pH 9.6. This suggests that dsb and not ssb are important as regards hydroxyl-radical-induced cell kill, as found for ionizing radiation. The correlation of induced dsb with lethal events showed that the predicted lethal effect of the H2O2-induced dsb was approximately 5 times less than that of X-ray-induced dsb. This is compared with data previously obtained which showed differences in the lethality of dsb with the quality of radiation (Prise et al. 1987).
Article
In bioassays conducted under controlled, comparable conditions, weak direct mutagenicity responses were observed for hydrogen peroxide in the standard (Ames test) agar plate incorporation bioassay with Salmonella typhimurium strains TA97, TA98, TA102, and TA1537, in a 20 min preincubation test with strains TA97, TA98, TA100, TA102, TA1537, and TA1538, and in a liquid incubation modification using strain TA1537. These results conclusively demonstrate that hydrogen peroxide is a weak mutagen, especially in strains that are sensitive to oxidative damage under suitable bioassay conditions.
Article
A population-based case-control study of cancer of oral cavity-oropharynx was conducted in the city of Torino, Italy, between 1982 and 1984. One hundred twenty-two cases (86 males and 36 females) and 606 controls (385 males and 221 females) were compared with respect to lifelong alcohol and tobacco consumption. A 4- to 6-fold increase in risk among subjects with medium or high tobacco consumption was observed, as well as a trend in increasing risk with duration and with earlier age at the start of smoking. Other findings included a sharp reduction in risk with cessation of smoking, no clear protective effect of usage of filter, no differences in risk according to color of tobacco, and a higher risk for cigar versus pipe/cigarette smokers. An effect of alcoholic beverages was found in subjects with an average daily consumption of 120 or more grams of alcohol, with a higher risk in beer drinkers. Among heavy consumers of alcohol and tobacco, risks of both oral and oropharyngeal cancer were very high. A positive association between oral cancer and low educational level, after adjustment for alcohol and tobacco, was found. Attributable risks for alcohol and tobacco in the population were 23% and 72% in men and 34% and 54% in women.
Article
The effect on oral cancer risk of different types of alcoholic beverage was investigated using data from a hospital-based case-control study. Owing to the small numbers of subjects drinking one beverage exclusively, it was necessary to classify drinkers as consumers of predominantly beer, wine, or hard liquor (i.e., more than 50% of their whiskey equivalents of alcohol derived from a specific beverage). The number of predominantly wine drinkers was too small to permit analysis. Logistic regression was used to obtain estimates of the risk associated with each predominant beverage, with adjustment for other risk factors and confounding variables. In males, the odds ratio for predominantly beer drinkers increased with increasing level of intake, reaching 4.87 (95% confidence interval: 2.51-9.46) in drinkers of 7+ oz. of whiskey equivalents/day. The odds ratio for predominantly hard liquor drinkers showed a similar increase, reaching 5.74 (95% confidence interval: 2.94-11.22) in predominantly hard liquor drinkers consuming 7+ oz. of whiskey equivalents/day, suggesting that the effect of these 2 major types of alcoholic beverage is of similar magnitude. The trends were less clearcut in women due to small numbers of drinkers.
Article
Aplastic phase serum from a patient with aplastic crisis of hereditary spherocytosis, which was demonstrated to contain human parvovirus, inhibited in vitro erythroid colony formation almost completely. Human parvovirus was resistant to heating for 30 min at 56 degrees C. The suppressive effect of the serum was completely abrogated by adding convalescent phase serum from another patient with aplastic crisis of hereditary spherocytosis. Some normal sera had similar neutralizing ability. The results suggested that aplastic crisis of a patient with hereditary spherocytosis is caused by human parvovirus and that the neutralizing test could offer a tool for predicting the future occurrence of aplastic crisis in the patients with chronic hemolytic anemia.
Article
Squamous cell carcinomas of the forestomach have been observed in many carcinogenicity studies in rodents, especially after oral or gavage exposure. The histopathological diagnosis of forestomach lesions and the relevance of the data for human risk estimation can be controversial. The pathological classification may be troublesome because of the low-grade malignancy and the pseudoepitheliomatous hyperplasia that may develop after ulceration and inflammation. For human risk estimation it is important to understand the mechanism of action; this is illustrated by examples using butylated hydroxyanisole, methyl bromide, and epichlorohydrin. Another feature that complicates risk estimation is the absence of a homologue for the forestomach in man. The potential risk from non-genotoxic forestomach carcinogens in man involves exposure of the mouth, pharynx, and esophagus at dose levels that exert irritating action. It is assumed that exposure to non-genotoxic chemicals at concentrations far below those having irritating potential is not hazardous to humans.
Article
The lethal and mutagenic effects of hydrogen peroxide were studied in exponentially growing cultures of Salmonella typhimurium strain TA102. Exposure of the cultures to non-lethal levels of sodium sulfide significantly increased the lethality and mutagenicity of hydrogen peroxide. The catalase activity was decreased in cells exposed to sodium sulfide, but there were no changes in the cellular levels of superoxide dismutase, glutathione reductase, or NADPH-dependent alkyl hydroperoxide reductase. Hydrogen peroxide-induced mutagenesis and killing of S. typhimurium strain TA102 in the presence of sulfide may in part be explained by an inactivation of catalase by sulfide.
Article
Ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide were tested for tumor-promoting activity in a two-stage stomach carcinogenesis experiment. Male outbred Wistar rats were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/liter) and a diet supplemented with 10% sodium chloride for 8 weeks. Thereafter, they were maintained on drinking water containing either 10% ethanol, 1% potassium metabisulfite, 0.5% formalin (formaldehyde) or 1% hydrogen peroxide for 32 weeks and then sacrificed for necropsy and histological examination. In the pylorus of the glandular stomach, potassium metabisulfite and formaldehyde significantly increased the incidence of adenocarcinoma after initiation with MNNG and sodium chloride. Hydrogen peroxide did not enhance the tumor yield, and ethanol showed a tendency to decrease neoplastic development. In the forestomach the incidence of squamous cell papilloma was significantly increased in the groups given hydrogen peroxide or formaldehyde, irrespective of prior initiation. Duodenal adenocarcinoma was induced by the initiation alone (10%) and the incidence was not affected by the subsequent treatments. The results indicate that potassium metabisulfite and formaldehyde both exert tumor-promoting activity in the rat glandular stomach.
Article
The usefulness of an in vitro test system to predict the inhibitory effect of beta-carotene on the genotoxic activity of carcinogens/mutagens was explored. To facilitate the comparison of data obtained from cultured cells (CHO) and from exfoliated human cells, endpoints were used which can be quantitated in both cell systems: the frequency of micronuclei for estimating the effect of genotoxic agents, and cellular levels of beta-carotene as a protective agent. In CHO cells, beta-carotene inhibited the clastogenic and micronucleus-forming effect of methyl methanesulfonate (MMS) and 4-nitroquinoline-1-oxide (4NQO), but had no protective action against gallic acid, tannic acid, and aqueous extract of areca nut or H2O2. The extent of inhibition depended on the ratio of beta-carotene to MMS. Doses of beta-carotene which exerted a protective effect in vitro ranged from approximately 2 to 5 ng per 10(6) CHO cells. Comparable levels of beta-carotene were previously found to reduce the frequency of micronucleated exfoliated cells from the buccal mucosa of tobacco and areca-nut chewers (Stich et al., 1984b).
Article
The effects of twice weekly topical applications of hydrogen peroxide on the buccal epithelium of Syrian hamsters were studied. Animals were treated either with hydrogen peroxide alone, with hydrogen peroxide and the carcinogen 9, 10-dimethyl-1,2-benzanthracene (DMBA), or with DMBA alone. In animals treated with 30% H2O2 alone, histopathologic examination after 22 weeks revealed hyperkeratosis and hyperplasia in all animals with hyperchromatic cells and mild dysplasia in four of nine: no tumors were seen. In animals treated with DMBA alone, three of seven (43%) developed epidermoid carcinoma, while six of 11 (55%) of animals treated with DMBA plus 3% hydrogen peroxide and five of five (100%) of animals treated with DMBA plus 30% hydrogen peroxide (P = 0.054) developed carcinoma. Thus, hydrogen peroxide can, by itself, induce pathologic changes frequently associated with preneoplastic lesions; it may also augment carcinogenesis associated with DMBA.
Article
Radicals generated by the peroxidase catalyzed oxidation of a wide variety of substrates oxidize GSH, NADH, or arachidonate with accompanying oxygen activation. Substrates studied include carcinogens, drugs, or xenobiotics. The effectiveness of the various radicals is partly related to their one-electron oxidation potential. High redox potential radicals were particularly effective at oxidizing these biomolecules. Low redox potential radicals did not react with GSH, NADH, or arachidonate, but can directly activate oxygen to form hydroxyl radicals or undergo scission to carbon radicals. The hydroxyl and carbon radicals have a high redox potential and readily oxidize biomolecules. DNA strand breakage also occurs with some high redox potential radicals, but DNA did not react with low redox potential radicals. The extensive binding of xenobiotics to DNA in the peroxidase system was attributed to noncovalent binding by polymeric products or covalent binding by the two electron oxidation product (formed by radical dismutation or oxidation). The latter can cause alkali labile DNA strand breaks. GSH conjugate formation was also attributed to the two electron oxidation product. Radicals have been trapped in intact cells and oxygen activation or lipid peroxidation has been demonstrated but it is still not clear whether the associated GSH oxidation, DNA strand breakage and cytotoxicity is the result of direct action by radicals. Indirect enzymic mechanisms for free radical mediated DNA strand breakage and cytotoxicity are discussed.
Article
The direct oxidation of PUFA by triplet oxygen is spin forbidden. The data reviewed indicate that lipid peroxidation is initiated by nonenzymatic and enzymatic reactions. One of the first steps in the initiation of lipid peroxidation in animal tissues is by the generation of a superoxide radical (see Figure 16), or its protonated molecule, the perhydroxyl radical. The latter could directly initiate PUFA peroxidation. Hydrogen peroxide which is produced by superoxide dismutation or by direct enzymatic production (amine oxidase, glucose oxidase, etc.) has a very crucial role in the initiation of lipid peroxidation. Hydrogen peroxide reduction by reduced transition metal generates hydroxyl radicals which oxidize every biological molecule. Hydrogen peroxide also activates myoglobin, hemoglobin, and other heme proteins to a compound containing iron at a higher oxidation state, Fe(IV) or Fe(V), which initiates lipid peroxidation even on membranes. Complexed iron could also be activated by O2- or by H2O2 to ferryl iron compound, which is supposed to initiate PUFA peroxidation. The presence of hydrogen peroxide, especially hydroperoxides, activates enzymes such as cyclooxygenase and lipoxygenase. These enzymes produce hydroperoxides and other physiological active compounds known as eicosanoids. Lipid peroxidation could also be initiated by other free radicals. The control of superoxide and perhydroxyl radical is done by SOD (a) (see Figure 16). Hydrogen peroxide is controlled in tissues by glutathione-peroxidase, which also affects the level of hydroperoxides (b). Hydrogen peroxide is decomposed also by catalase (b). Caeruloplasmin in extracellular fluids prevents the formation of free reduced iron ions which could decompose hydrogen peroxide to hydroxyl radical (c). Hydroxyl radical attacks on target lipid molecules could be prevented by hydroxyl radical scavengers, such as mannitol, glucose, and formate (d). Reduced compounds and antioxidants (ascorbic acid, alpha-tocopherol, polyphenols, etc.) (e) prevent initiation of lipid peroxidation by activated heme proteins, ferryl ion, and cyclo- and lipoxygenase. In addition, cyclooxygenase is inhibited by aspirin and nonsteroid drugs, such as indomethacin (f). The classical soybean lipoxygenase inhibitors are antioxidants, such as nordihydroguaiaretic acid (NDGA) and others, and the substrate analog 5,8,11,14 eicosatetraynoic acid (ETYA), which also inhibit cyclooxygenase (g). In food, lipoxygenase is inhibited by blanching. Initiation of lipid peroxidation was derived also by free radicals, such as NO2. or CCl3OO. This process could be controlled by antioxidants (e).(ABSTRACT TRUNCATED AT 400 WORDS)
Article
Hydrogen peroxide (H2O2) was investigated for its potential to induce gene mutations in V79 Chinese hamster cells. Exposure of 2-3 X 10(6) cells/100-mm dish to 0.5-4.0 mM H2O2 for 1 h resulted in a concentration-dependent increase in the frequency of 6-thioguanine-resistant clones. At 4 mM H2O2 the mutation frequency was increased about 6-fold above that in controls and survival of the cells was reduced by 50%. Cytotoxicity was markedly increased at lower cell densities. When only 100-200 cells/100-mm dish were exposed to H2O2 for 1 h, 50% were killed at an H2O2 concentration as low as 60 microM. The results show that mutagenicity of H2O2 in mammalian cells in vitro has escaped attention previously because the concentrations tested were too low, presumably because the likely toxicity of H2O2 to V79 cells treated at high cell densities was overestimated.
Article
Hydrogen peroxide (H2O2) and caffeine were examined for their capacity for inducing SCEs and mutations at the HPRT locus in V79 Chinese hamster cells. Although, under standard conditions, both substances induced SCEs neither caused gene mutations. The SCE induction by both H2O2 and caffeine is influenced by BrdUrd substitution. Whereas H2O2 also induces lesions leading to SCEs in normal DNA, the SCe induction by caffeine depends on the replication of BrdUrd-substituted DNA. In cells with BrdUrd-substituted DNA, H2O2 induces mutations at the HPRT locus parallel to its SCE induction, whereas caffeine in the presence of BrdUrd only has an influence on the SCE rate. It is shown that the experimental conditions of the two test systems can play a decisive role when contradictory results are obtained.
Article
The influence of the nuclear ADP-ribosyltransferase inhibitor 3-aminobenzamide on the DNA strand-break rejoining kinetics and cytotoxicity in Chinese hamster ovary cells following H2O2 treatment was investigated. For the DNA damage studies, cells were treated on ice with H2O2 (0-20 microM) for 1 h in serum-free medium, after which the H2O2 was removed and the cells were allowed to repair their damage in complete medium at 37 degrees C in the presence or absence of 3-aminobenzamide (5 mM) for periods up to 2 h. The DNA strand breaks remaining as a function of time were then estimated by alkaline elution. A linear relationship between the H2O2 concentration and the initial level of DNA single-strand breaks (zero time allowed for repair) was observed. No double-strand breaks or DNA-protein cross-links were detected at these doses. The rejoining of single-strand breaks after H2O2 (20 microM) alone was characterized by a single exponential process with a t1/2 of approx. 5 min. However, in the presence of 3-aminobenzamide, rejoining was much slower and biphasic, with t1/2 of approx. 10 and 36 min. The inhibitory action of 3-aminobenzamide was concentration-dependent and completely reversible in that, when the 3-aminobenzamide was removed from the treated cultures, the strand-break rejoining kinetics rapidly returned to the t1/2 of 5 min typical of H2O2 alone. Considerably higher concentrations of H2O2 (up to 600 microM) were required for cell killing compared to the DNA damage studies. Cell killing by H2O2 alone was characterized by a shoulderless, exponential survival curve (D0 = 880 microM). The cytotoxicity was potentiated when the cells were treated with 3-aminobenzamide (5 mM) for 1 h after the H2O2 treatment; the survival curve with 3-aminobenzamide also assumed a biphasic character (D0 of 212 microM and 520 microM). These results are consistent with the theory that OH.-induced single-strand breaks do not normally represent lethal lesions to the cell because of their rapid, efficient repair. However, interference with these repair processes (in this case by 3-aminobenzamide) can alter this relationship, possibly allowing lesion fixation.
Article
The cytogenetic effect of hydrogen peroxide (H2O2) was investigated in human embryonic fibroblasts. Chromosome-type aberrations were found together with chromatid-type aberrations in metaphase cells harvested 24 h after a single 10-min treatment with 10(-5)-10(-3) M H2O2 in 0.9% NaCl solution. The chromosome-type aberrations were observed to be predominantly dicentrics and deletions. Both types of aberration showed a dose-response relationship to the dose of H2O2 over the range of 10(-5)-1.5 X 10(-4) M H2O2. The intercellular distribution of dicentrics showed a Poisson distribution. Centric and acentric rings and abnormal monocentrics were a minor fraction of the chromosome-type aberrations. The chromatid-type aberrations observed, such as breaks, exchanges and gaps, showed no dose-response relationship. The frequency of isochromatid breaks was higher than that of chromatid breaks and approximately 70% of the isochromatid breaks were found in the centromeric or pericentromeric region. The intercellular distribution of chromatid exchanges showed an over-dispersed distribution. The generation of aberrations by H2O2 was effectively suppressed by catalase and several scavengers of hydroxyl radicals (.OH) such as ethanol, dimethyl sulfoxide (DMSO) and mannitol. This result suggest that .OH plays an essential role in the generation of the chromosome aberrations by H2O2.