Tobacco Smoke Induces Ventricular Remodeling Associated with an Increase in NADPH Oxidase Activity

Background: Recent studies have assessed the direct effects of smoking on cardiac remodeling and function. However, the mechanisms of these alterations remain unknown. The aim of this study was to investigate de role of cardiac NADPH oxidase and antioxidant enzyme system on ventricular remodeling induced by tobacco smoke. Methods: Male Wistar rats that weighed 200-230 g were divided into a control group (C) and an experimental group that was exposed to tobacco smoke for a period of two months (ETS). After the two-month exposure period, morphological, biochemical and functional analyses were performed. Results: The myocyte cross-sectional area and left ventricle end-diastolic dimension was increased 16.2% and 33.7%, respectively, in the ETS group. The interstitial collagen volume fraction was also higher in ETS group compared to the controls. In addition to these morphological changes, the ejection fraction and fractional shortening were decreased in the ETS group. Importantly, these alterations were related to augmented heart oxidative stress, which was characterized by an increase in NADPH oxidase activity, increased levels of lipid hydroperoxide and depletion of antioxidant enzymes (e.g., catalase, superoxide dismutase and glutathione peroxidase). In addition, cardiac levels of IFN-gamma, TNF-alpha and IL-10 were not different between the groups. Conclusion: Cardiac alterations that are induced by smoking are associated with increased NADPH oxidase activity, suggesting that this pathway plays a role in the ventricular remodeling induced by exposure to tobacco smoke. Copyright (C) 2011 S. Karger AG, Basel

An Inhalation Chamber Model for Controlled Studies of Tobacco Smoke Toxicity in Rodents

Introduction: Smoking is a serious worldwide public health problem. Animal models act as a bridge between laboratory and human studies. The models applied are difficult to reproduce because of the use of different types of inhalation chambers and mainly because of the lack of continuous monitoring of smoke concentration. Objective: To develop an inhalation chamber for rats (with only the nose exposed) in which the amount of carbon monoxide (CO) can be maintained and monitored constantly. Material and methods: Male Wistar rats weighing 250 g were exposed to 50 ppm CO produced by the smoke from a filter-free cigarette. The animals were submitted to a single 2-h exposure and then sacrificed at 0, 4, 24 and 48 h. The control group was left restrained inside the small perpendicular chambers, receiving only 5 L/min of compressed air. Results: The model was able to increase HbCO levels immediately after the end of exposure (p < 0.001). with a decrease being observed from 2 h onwards when compared to the levels of the control group. Plasma cotinine increased immediately after exposure, and showed still detectable levels at 2 and 4 h (p < 0.05). Conclusion: We conclude that the presented inhalation chamber system is able to maintain a controlled CO concentration in a model in which small animals are exposed to the inhalation of cigarette smoke, permitting well-controlled studies, as well as investigations involving other toxic gases and air pollutants. (C) 2008 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.

Early Changes in Gene Expression Induced by Tobacco Smoke: Evidence for the Importance of Estrogen within Lung Tissue

Lung cancer is the leading cause of cancer deaths in the United States, surpassing breast cancer as the primary cause of cancer-related mortality in women. The goal of the present study was to identify early molecular changes in the lung induced by exposure to tobacco smoke and thus identify potential targets for chemoprevention. Female A/J mice were exposed to either tobacco smoke or HEPA-filtered air via a whole-body exposure chamber (6 h/d, 5 d/wk for 3, 8, and 20 weeks). Gene expression profiles of lung tissue from control and smoke-exposed animals were established using a 15K cDNA microarray. Cytochrome P450 1b1, a phase I enzyme involved in both the metabolism of xenobiotics and the 4-hydroxylation of 17 beta-estradiol (E(2)), was modulated to the greatest extent following smoke exposure. A panel of 10 genes were found to be differentially expressed in control and smoke-exposed lung tissues at 3, 8, and 20 weeks (P < 0.001). The interaction network of these differentially expressed genes revealed new pathways modulated by short-term smoke exposure, including estrogen metabolism. In addition, E(2) was detected within murine lung tissue by gas chromatography-coupled mass spectrometry and immunohistochemistry. Identification of the early molecular events that contribute to lung tumor formation is anticipated to lead to the development of promising targeted chemopreventive therapies. In conclusion, the presence of E2 within lung tissue when combined with the modulation of cytochrome P450 1b1 and other estrogen metabolism genes by tobacco smoke provides novel insight into a possible role for estrogens in lung cancer. Cancer Prev Res; 3(6); 707-17. (C) 2010 AACR.

The effect of Sao Paulo`s smoke-free legislation on carbon monoxide concentration in hospitality venues and their workers

Background Studies have shown that there is no safe level of secondhand smoke (SHS) exposure and there is a close link between SHS and the risk of coronary heart disease and stroke. Carbon monoxide (CO) is one of the most important components present in SHS. Objective To evaluate the impact of the smoking ban law in the city of Sao Paulo, Brazil, on the CO concentration in restaurants, bars, night clubs and similar venues and in their workers. Methods In the present study we measured CO concentration in 585 hospitality venues. CO concentration was measured in different environments (indoor, semi-open and open areas) from visited venues, as well as, in the exhaled air from approximately 627 workers of such venues. Measurements were performed twice, before and 12 weeks after the law implementation. In addition, the quality of the air in the city during the same period of our study was verified. Results The CO concentration pre-ban and pot-ban in hospitality venues was indoor area 4.57 (3.70) ppm vs 1.35 (1.66) ppm (p<0.0001); semi-open 3.79 (2.49) ppm vs 1.16 (1.14) ppm (p<0.0001); open area 3.31 (2.2) ppm vs 1.31 (1.39) ppm (p<0.0001); smoking employees 15.78 (9.76) ppm vs 11.50 (7.53) ppm (p<0.0001) and non-smoking employees 6.88 (5.32) ppm vs 3.50 (2.21) ppm (p<0.0001). The average CO concentration measured in the city was lower than 1 ppm during both pre-ban and post-ban periods. Conclusion Sao Paulos smoking-free legislation reduced significantly the CO concentration in hospitality venues and in their workers, whether they smoke or not.

Effects of sidestream cigarette smoke exposure on baroreflex components in spontaneously hypertensive rats

We evaluated short-term effects of sidestream cigarette smoke (SSCS) exposure on baroreflex function in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) normotensive rats. Rats were exposed to SSCS during three weeks, 180min, five days per week, in a concentration of carbon monoxide (CO) between 100 and 300ppm. We observed that SSCS exposure increased tachycardic peak and heart rate range while it attenuated bradycardic reflex in WKY. In respect to SHR, SSCS also increased tachycardic peak. Taken together, our data suggests that three weeks of exposure to SSCS affects the sympathetic and parasympathetic component of the baroreflex in normotensive WKY while it tended to affect the sympathetic component in SHR.

Cigarette smoke exposure impairs respiratory epithelial ciliogenesis

Background: Cigarette smoke exposure is considered an important negative prognostic factor for chronic rhinosinusitis (CRS) patients. However, there is no clear mechanistic evidence implicating cigarette smoke exposure in the poor clinical evolution of the disease or in the maintenance of the inflammatory state characterizing CRS. This study aimed to evaluate the effects of cigarette smoke exposure on respiratory cilia differentiation. Methods: Monse nasal septal epithelium cultures grown at an air-liquid interface were used as a model of respiratory epithelium. After 5 days of cell growth, cultures were exposed to air on the apical surface. Additionally, cigarette smoke condensate (CSC; the particulate phase of tobacco smoke) or cigarette smoke extract (CSE; the volatile phase) Were diluted in the basolateral compartment in different concentrations. After 15 days of continuous exposure, scanning electron microscopy and immunofluorescence for type IV tubulin were used to determine presence and maturation of cilia. Transepithelial resistance was also recorded to evaluate confluence and physiological barrier integrity. Results: CSC and CSE impair ciliogenesis in a dose-dependent manner with notable effects in concentrations higher than 30 mu g/mL, yielding >70% nonciliation and shorter cilia compared With control. No statistical difference on transepithelial resistance was evident. Conclusion: CSC and CSE exposure negatively impacts ciliogenesis of respiratory cells at concentrations not effecting transepithelial resistance. The impairment on ciliogenesis reduce the mucociliary clearance apparatuts after injury and/or infection and may explain the poor response to therapy for CRS patients exposed to tobacco smoke.

Prevalência e fatores associados ao tabagismo em escolares da Região Sul do Brasil

OBJETIVO: Estimar a prevalência do tabagismo em estudantes e os fatores associados.MÉTODOS: Foram utilizados dados secundários, provenientes do inquérito Vigescola realizado em Curitiba (PR), Florianópolis (SC) e Porto Alegre (RS) em 2002 e 2004. A amostra compreendeu 3.690 escolares de 13 a 15 anos, cursando as sétima e oitava séries do ensino fundamental e primeira do ensino médio, em escolas públicas e privadas. Para a análise dos resultados foram estimadas proporções ponderadas, odds ratio (OR), e utilizada a técnica de regressão logística múltipla.RESULTADOS: As taxas de prevalência de tabagismo corresponderam a 10,7 por cento (IC 95 por cento: 10,2;11,3) em Florianópolis, 12,6 por cento (IC 95 por cento: 12,4;12,9) em Curitiba e 17,7 por cento (IC 95 por cento: 17,4;18,0) em Porto Alegre. Os fatores associados ao tabagismo em escolares em Curitiba foram: sexo feminino (OR=1,49), pai fumante (OR=1,59), amigos fumantes (OR=3,46), exposição à fumaça do tabaco fora de casa (OR=3,26) e possuir algum objeto com logotipo de marca de cigarro (OR=3,29). Em Florianópolis, as variáveis associadas ao tabagismo foram escolares do sexo feminino (OR=1,26), ter amigos fumantes (OR=9,31), exposição à fumaça do tabaco em casa (OR=2,03) e fora de casa (OR=1,45) e ter visto propaganda em cartazes (OR=1,82). Em Porto Alegre, as variáveis que estiveram associadas com o uso de tabaco pelos escolares foram sexo feminino (OR=1,57), idade entre 14 anos (OR=1,77) e 15 anos (OR=2,89), amigos fumantes (OR=9,12), exposição à fumaça do tabaco em casa (OR=1,87) e fora de casa (OR=1,77) e possuir algo com logotipo de marca de cigarro (OR=2,83).CONCLUSÕES: Há elevada prevalência de tabagismo entre escolares de 13 a 15 anos, cujos fatores significativamente associados comuns às três capitais são: ter amigos fumantes e estar exposto à fumaça ambiental fora de casa

Tabagismo e câncer no Brasil: evidências e perspectivas

Neste artigo analisa-se a tendência temporal da prevalência do tabagismo no Brasil, bem como as assimetrias da prevalência de acordo com as regiões do país, a idade, o gênero e o nível socioeconômico da população. Desde o estabelecimento da relação entre tabagismo e câncer de pulmão há 60 anos, o número de tumores malignos com evidências de associação causal com o tabagismo ascendeu a vinte. O declínio da prevalência do tabagismo na população brasileira tem sido constante desde o final da década de 80. Até 2003, foi mais intenso entre os homens. A partir daquele ano, a queda tornou-se mais pronunciada entre as mulheres. As mais altas prevalências de tabagismo encontram-se no Sudeste e Sul, as duas regiões com maiores incidências de neoplasias estritamente relacionadas ao tabaco (cavidade oral, esôfago e pulmão). A exposição ambiental à fumaça do tabaco também foi examinada considerando-se os efeitos para os adultos não fumantes, que apresentam maior risco de tumores de pulmão, laringe e faringe, e entre crianças de pais fumantes, suscetíveis ao risco de hepatoblastoma e leucemia linfocítica aguda. Apesar do incontestável sucesso da política de controle do tabagismo no país, as ações de prevenção devem considerar que as parcelas da população com piores condições socioeconômicas e com baixo nível educacional são as que apresentam taxas mais altas de prevalência de tabagismo. Dentro destes segmentos populacionais os adolescentes representam uma prioridade

CYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor outcome in head and neck squamous cell carcinoma patients

Head and neck squamous cell carcinoma (HNSCC) is associated with environmental factors, especially tobacco and alcohol consumption. Most of the carcinogens present in tobacco smoke are converted into DNA-reactive metabolites by cytochrome P450 (CYPs) enzymes and detoxification of these substances is performed by glutathione S-transferases (GSTs). It has been suggested that genetic alterations, such as polymorphisms, play an important role in tumorigenesis and HNSCC progression. The aim of this study was to investigate CYP1A1, CYP1A2, CYP2E1, GSTM1, and GSTT1 polymorphisms as risk factors in HNSCC and their association with clinicopathologic data. The patients comprised 153 individuals with HNSCC (cases) and 145 with no current or previous diagnosis of cancer (controls). Genotyping of the single nucleotide polymorphisms (SNPs) of the CYP1A1, CYP1A2, and CYP2E1 genes was performed by PCR-RFLP and the GSTM1 and GSTT1 copy number polymorphisms (CNPs) were analyzed by PCR-multiplex. As expected, a significant difference was detected for tobacco and alcohol consumption between cases and controls (P < 0.001). It was observed that the CYP1A2*1D (OR = 16.24) variant and GSTM1 null alleles (OR = 0.02) confer increased risk of HNSCC development (P < 0.001). In addition, head and neck cancer alcohol consumers were more frequently associated with the CYP2E1*5B variant allele than control alcohol users (P < 0.0001, OR = 190.6). The CYP1A2*1C polymorphism was associated with tumor recurrence (log-rank test, P = 0.0161). The CYP2E1*5B and GSTM1 null alleles were significantly associated with advanced clinical stages (T3 + T4; P = 0.022 and P = 0.028, respectively). Overall, the findings suggested that the genetic polymorphisms studied are predictors of risk and are also associated with tumor recurrence, since they are important for determining the parameters associated with tumor progression and poor outcomes in HNSCC. (C) 2009 Elsevier Ltd. All rights reserved.

Marijuana Smoking and the Risk of Head and Neck Cancer: Pooled Analysis in the INHANCE Consortium

Background: Marijuana contains carcinogens similar to tobacco smoke and has been suggested by relatively small studies to increase the risk of head and neck cancer (HNC). Because tobacco is a major risk factor for HNC, large studies with substantial numbers of never tobacco users could help to clarify whether marijuana smoking is independently associated with HNC risk. Methods: We pooled self-reported interview data on marijuana smoking and known HNC risk factors on 4,029 HNC cases and 5,015 controls from five case-control studies within the INHANCE Consortium. Subanalyses were conducted among never tobacco users (493 cases and 1,813 controls) and among individuals who did not consume alcohol or smoke tobacco (237 cases and 887 controls). Results: The risk of HNC was not elevated by ever marijuana smoking [odds ratio (OR), 0.88; 95% confidence intervals (95% Cl), 0.67-1.16], and there was no increasing risk associated with increasing frequency, duration, or cumulative consumption of marijuana smoking. An increased risk of HNC associated with marijuana use was not detected among never tobacco users (OR, 0.93; 95% Cl, 0.63-1.37; three studies) nor among individuals who did not drink alcohol and smoke tobacco (OR, 1.06; 95% Cl, 0.47-2.38; two studies). Conclusion: Our results are consistent with the notion that infrequent marijuana smoking does not confer a risk of these malignancies. Nonetheless, because the prevalence of frequent marijuana smoking was low in most of the contributing studies, we could not rule out a moderately increased risk, particularly among subgroups without exposure to tobacco and alcohol. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1544-51)

Involuntary smoking and head and neck cancer risk: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium

Although active tobacco smoking has been identified as a major risk factor for head and neck cancer, involuntary smoking has not been adequately evaluated because of the relatively low statistical power in previous studies. We took advantage of data pooled in the International Head and Neck Cancer Epidemiology Consortium to evaluate the role of involuntary smoking in head and neck carcinogenesis. Involuntary smoking exposure data were pooled across six case-control studies in Central Europe, Latin America, and the United States. Adjusted odds ratios (OR) and 95% confidence interval (95% CI) were estimated for 542 cases and 2,197 controls who reported never using tobacco, and the heterogeneity among the study-specific ORs was assessed. In addition, stratified analyses were done by subsite. No effect of ever involuntary smoking exposure either at home or at work was observed for head and neck cancer overall. However, long duration of involuntary smoking exposure at home and at work was associated with an increased risk (OR for >15 years at home, 1.60; 95% CI, 1.12-2.28; P(trend) <0-01; OR for >15 years at work, 1.55; 95% CI, 1.04-2.30; P(trend) = 0.13). The effect of duration of involuntary smoking exposure at home was stronger for pharyngeal and laryngeal cancers than for other subsites. An association between involuntary smoking exposure and the risk of head and neck cancer, particularly pharyngeal and laryngeal cancers, was observed for long duration of exposure. These results are consistent with those for active smoking and suggest that elimination of involuntary smoking exposure might reduce head and neck cancer risk among never smokers.

[(13)C(2)]- Acetaldehyde Promotes Unequivocal Formation of 1,N(2)-Propano-2 `-deoxyguanosine in Human Cells

Acetaldehyde is an environmentally widespread genotoxic aldehyde present in tobacco smoke, vehicle exhaust and several food products. Endogenously, acetaldehyde is produced by the metabolic oxidation of ethanol by hepatic NAD-dependent alcohol dehydrogenase and during threonine catabolism. The formation of DNA adducts has been regarded as a critical factor in the mechanisms of acetaldehyde mutagenicity and carcinogenesis. Acetaldehyde reacts with 2`-deoxyguanosine in DNA to form primarily N(2)-ethylidene-2`-deoxyguanosine. The subsequent reaction of N(2)-ethylidenedGuo with another molecule of acetaldehyde gives rise to 1,N(2)-propano-2`-deoxyguanosine (1,N(2)-propanodGuo), an adduct also found as a product of the crotonaldehyde reaction with dGuo. However, adducts resulting from the reaction of more than one molecule of acetaldehyde in vivo are still controversial. In this study, the unequivocal formation of 1,N(2)-propanodGuo by acetaldehyde was assessed in human cells via treatment with [(13)C(2)]-acetaldehyde. Detection of labeled 1,N(2)-propanodGuo was performed by HPLC/MS/MS. Upon acetaldehyde exposure (703 mu M), increased levels of both 1,N(2)-etheno-2`-deoxyguanosine (1,N(2)-epsilon dGuo), which is produced from alpha,beta-unsaturated aldehydes formed during the lipid peroxidation process, and 1,N(2)-propanodGuo were observed. The unequivocal formation of 1,N(2)-propanodGuo in cells exposed to this aldehyde can be used to elucidate the mechanisms associated with acetaldehyde exposure and cancer risk.

Effects of Pentoxyfilline and Heparin on Reperfusion Injury Island Skin Flaps in Rats Exposed to Tobacco

Background. Ischemia-reperfusion injury is believed to be a major cause of transferred skin flap failure. Cigarette smoking is known to be associated with endogenous antioxidant depletion, hypercoagulability, and cutaneous vasoconstriction. This investigation was carried out to study possible effects of pentoxyfilline or heparin on rat skin reperfusion injury under tobacco exposure. Materials and Methods. Thirty-six rats were randomized into two major groups: 18 were exposed to cigarette smoke during a 4 wk period prior to surgery; the remaining 18 underwent a sham smoking procedure. Each group was further divided into three equal subgroups: heparin, pentoxyfilline, and saline solution. One identical skin flap was raised in each animal. The vasculature of the flap was clamped for 3 h and reperfused for 5 min. A venous blood sample was obtained from the flap after reperfusion for serum malondialdehyde (MDA) and myeloperoxidase (MPO) analysis. Flap survival was assessed 7 d after the procedure. Results. The lipid peroxidation levels and flap necrosis were significantly higher in the cigarette-smoking group skin flaps. There was also a decrease of MPO activity in this group compared with the nonsmoking group. Heparin-treated rats had significantly lower MDA levels and showed the most viable percent area among smoking rats. Conclusions. These data suggest that heparin had a significant beneficial effect both on flap survival and on the lipid peroxidation reduction after smoke exposure in the rat axial-pattern skin flap subjected to ischemia and reperfusion injury. Pharmacologic therapy may represent an alternative way to counteract tobacco effects in flap surgery in emergency situations. (C) 2010 Elsevier Inc. All rights reserved.

Deposition of Lead and Cadmium Released by Cigarette Smoke in Dental Structures and Resin Composite

Cigarette smoke is a significant source of cadmium, lead, and toxic elements, which are absorbed into the human organism. In this context, the aim of this study was to investigate in vitro the presence of toxic elements, cadmium, and lead deriving from cigarette smoke in the resin composite, dentine, and dental enamel. Eight cylindrical specimens were fabricated from resin composite, bovine enamel, and root dentin fragments that were wet ground and polished with abrasive paper to obtain sections with 6-mm diameter and 2-mm thickness. All specimens were exposed to the smoke of 10 cigarettes/day during 8 days. After the simulation of the cigarette smoke, the specimens were examined with scanning electron microscopy (SEM) and the energy-dispersive X-ray analysis. In the photomicrographic analysis in SEM, no morphological alterations were found; however, the microanalysis identified the presence of cadmium, arsenic, and lead in the different specimens. These findings suggest that the deposition of these elements derived from cigarette smoke could be favored by dental structures and resin composite. Microsc. Res. Tech. 74:287-291, 2011. (C) 2010 Wiley-Liss, Inc.

Polyamine patterns in haploid and diploid tobacco tissues and in vitro cultures

The aim of this work was to determine PAs levels in pith tissues and callus cultures from haploid and diploid tobacco plants, explanted from the apical and basal regions of the stem. These explants were cultured in an RM-64 medium supplied with IAA and kinetin, under light or in the dark, during successive subcultures. PAs levels followed a basipetal decrease in diploid and an increase in haploid, pith tissues. A similar pattern of total PAs (free + conjugated) was observed for the callus of diploid and haploid plants maintained in the light, and for the haploid callus in the dark, whereas the diploid callus in the dark showed a constant increase in total PAs levels until the end of culture. The PA increase in the diploid callus in the dark was related to free Put levels increase. The ploidy status of the plants could express different PA gradients together with the plant pith and in vitro callus cultures.