Toxicity Of Cigarette Smoke Research Articles

Nicotine Component of Cigarette Smoke Extract (CSE) Decreases the Cytotoxicity of CSE in BEAS-2B Cells Stably Expressing Human Cytochrome P450 2A13.

Cytochrome P450 2A13 (CYP2A13), an extrahepatic enzyme mainly expressed in the human respiratory system, has been reported to mediate the metabolism and toxicity of cigarette smoke. We previously found that nicotine inhibited 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism by CYP2A13, but its influence on other components of cigarette smoke remains unclear. The nicotine component of cigarette smoke extract (CSE) was separated, purified, and identified using high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), splitting CSE into a nicotine section (CSE-N) and nicotine-free section (CSE-O). Cell viability and apoptosis by Cell Counting Kit-8 (CCK-8) and flow cytometry assays were conducted on immortalized human bronchial epithelial (BEAS-2B) cells stably expressing CYP2A13 (B-2A13) or vector (B-V), respectively. Interestingly, CSE and CSE-O were toxic to BEAS-2B cells whereas CSE-N showed less cytotoxicity. CSE-O was more toxic to B-2A13 cells than to B-V cells (IC50 of 2.49% vs. 7.06%), which was flatted by 8-methoxypsoralen (8-MOP), a CYP inhibitor. CSE-O rather than CSE or CSE-N increased apoptosis of B-2A13 cells rather than B-V cells. Accordingly, compared to CSE-N and CSE, CSE-O significantly changed the expression of three pairs of pro- and anti-apoptotic proteins, Bcl-2 Associated X Protein/B cell lymphoma-2 (Bax/Bcl-2), Cleaved Poly (Adenosine Diphosphate-Ribose) Polymerase/Poly (Adenosine Diphosphate-Ribose) Polymerase (C-PARP/PARP), and C-caspase-3/caspase-3, in B-2A13 cells. In addition, recombination of CSE-N and CSE-O (CSE-O/N) showed similar cytotoxicity and apoptosis to the original CSE. These results demonstrate that the nicotine component decreases the metabolic activation of CYP2A13 to CSE and aids in understanding the critical role of CYP2A13 in human respiratory diseases caused by cigarette smoking.

The effects of cigarette smoke nanoparticles in the colorectal carcinogenesis of wistar rats

Smoking cigarette is one of risk factors for developing colorectal carcinoma. Various researches have been made to suppress the toxicity of cigarette smoke. One of such effort is to reduce the size of cigarette smoke particles using nano water solution containing aromatic groups and EDTA. This study aims to assess the effects of this cigarette smoke nanoparticle regarding colorectal carcinogenesis. The experimental study was carried out with sequential post test only control group design. Thirty Wistar rats were divided into 3 groups: exposure to cigarettes smoke, exposure to smoke of cigarettes containing nano water solution and control for 14 weeks and 28 weeks. Colorectal epithelial morphology was assessed on the histopathology examination, whereas the expression of APC, KRAS, MSH2, MLH1, and p53 was assessed on immunohistochemistry procedure. Our results showed that cigarette smoke nanoparticles had better effects regarding colorectal epithelial morphology, especially through the increased expression of APC.

A randomised, controlled, two-Centre open-label study in healthy Japanese subjects to evaluate the effect on biomarkers of exposure of switching from a conventional cigarette to a tobacco heating product

BackgroundSmoking is a leading cause of numerous human disorders including lung cancer, chronic obstructive pulmonary disease, and atherosclerotic cardiovascular disease. The development of modified risk tobacco products (MRTPs) has been suggested as a possible way to reduce the risks of tobacco smoking by reducing exposure to cigarette smoke toxicants. This study is designed to investigate whether biomarkers of such exposure are reduced when smokers switch from smoking commercial cigarettes to using either a novel or a commercially-available tobacco heating product (THP).Design and MethodsThis study will assess biomarkers of exposure in current smokers who either remain smoking, switch to THP use, or quit all tobacco use completely, for 5 days. The study is an in-clinic (confinement) two-centre, randomised controlled clinical study with a forced-switching design.Subjects of either gender will be aged 23–55 years (minimum legal smoking age plus 3 years), of Japanese origin and with a verified smoking status (assessed by exhaled breath carbon monoxide and urinary cotinine levels). Subjects will have a usual brand cigarette within the International Organisation for Standardisation (ISO) tar band of 6-8 mg and will be judged to be healthy by medical history, physical examination, vital signs, electrocardiography (ECG), clinical biochemistry and lung function tests.The primary objective of this study is to assess changes within groups in selected biomarkers of exposure (BoE) and of biological effect (BoBE) after a forced switch from a commercial control cigarette to either a menthol or a non-menthol THP. Secondary objectives are to assess between-group differences, to determine nicotine pharmacokinetics for cigarettes and THPs, to assess subject’s satisfaction with the study products, and to monitor additional endpoints related to safety and product use.DiscussionData from this study will advance our scientific understanding of the changes in exposure to cigarette smoke toxicants in smokers who switch to using a THP.Trial registrationsUMIN000024988 (25th November 2016); ISRCTN14301360 (14th December 2016)

A novel hybrid tobacco product that delivers a tobacco flavour note with vapour aerosol (Part 1): Product operation and preliminary aerosol chemistry assessment

Vapour products have demonstrated potential to be a lower-risk alternative to cigarettes. The present study describes a novel hybrid tobacco product that combines a warm aerosol stream generated by an electronic vaporisation mechanism with tobacco top flavour from cut tobacco. During operation, the aerosol stream released from the vapour cartomiser is passed through a bed of blended cut tobacco by the puffing flow, elevating the tobacco temperature and eluting volatile tobacco flavour components. A preliminary but comprehensive analysis of the aerosol composition of the hybrid tobacco product found that emissions were dominated by the control vapour formulation. In non-targeted chemical screening, no detectable difference in GC scans was observed between the hybrid tobacco product and the control vapour product. However, a sensorially elevated tobacco flavour was confirmed by a consumer sensory panel (P < 0.05). In a targeted analysis of 113 compounds, either identified by regulatory bodies as potential toxicants in cigarette smoke or formed from electronic vapour products, only 26 were quantified. The novel action of tobacco heating and liquid aerosolisation produced classes and levels of toxicants that were similar to those of the control vapour product, but much lower than those of a Kentucky 3R4F reference cigarette. For nine toxicants mandated by the WHO Study Group on Tobacco Product Regulation for reduction in cigarette emissions, the levels were 91%–99% lower per puff in the hybrid tobacco product aerosol than in 3R4F smoke. Overall, the novel hybrid tobacco product provides a sensorially enhanced tobacco flavour, but maintains a toxicant profile similar to its parent vapour product with relatively low levels of known cigarette smoke toxicants.

Impact assessment of WHO TobReg proposals for mandated lowering of selected mainstream cigarette smoke toxicants

The WHO Tobacco Product Regulation Study Group (TobReg) has proposed three regulatory models for cigarettes, each creating mandatory limits for emissions of nine smoke toxicants. One approach proposes country-specific limits, using median or 1.25× median toxicant/nicotine emission ratios. A second model provides fixed toxicant-ratio limits. The third model limits were three times the lowest toxicant emission on a market. Currently, the practical implications of these models are largely unknown.An impact assessment was conducted using cigarette data from 79 countries to identify four diverse test markets. We sampled all products from each market but limited product availability led to incomplete (80–97%) sourcing. Analysis showed that the country-specific model led to diverse (up to threefold) toxicant limits across the four markets. 70%–80% of products were non-compliant, rising to 100% in some countries with the second and the third models. With each regulatory model the main drivers of non-compliance were the tobacco-specific nitrosamines, the simultaneous application of limits for nine poorly correlated smoke toxicants, and analytical variability. Use of nicotine ratios led to compliance of some high toxicant emission products due to high nicotine emissions.Our findings suggest that these proposals would have greater impact on global markets than TobReg's stated aims.

The impact of tobacco additives on cigarette smoke toxicity: a critical appraisal of tobacco industry studies.

Cigarette production involves a number of substances and materials other than just tobacco, paper and a filter. Tobacco additives include flavorings, enhancers, humectants, sugars, and ammonium compounds. Although companies maintain that tobacco additives do not enhance smoke toxicity and do not make cigarettes more attractive or addictive, these claims are questioned by independent researchers. This study reviewed the studies on the effects of tobacco additives on smoke chemistry and toxicity. Tobacco additives lead to higher levels of formaldehyde and minor changes in other smoke analytes. Toxicological studies (bacterial mutagenicity and mammalian cytoxicity tests, rat 90 days inhalation studies and bone-marrow cell micronucleus assays) found that tobacco additives did not enhance smoke toxicity. Rodent assays, however, poorly predicted carcinogenicity of tobacco smoke, and were clearly underpowered to disclose small albeit toxicologically relevant differences between test (with tobacco additives) and control (without tobacco additives) cigarettes. This literature review led to the conclusion that the impact of tobacco additives on tobacco smoke harmfulness remains unclear.

Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study.

Electronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants. We measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance. In total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p < .05). After 1 week, the greatest percentage reductions in biomarkers levels were observed for metabolites of 1,3-butadiene, benzene, and acrylonitrile. Total NNAL, a metabolite of NNK, declined by 57% and 64% after 1 and 2 weeks, respectively, while 3-hydroxyfluorene levels declined by 46% at week 1, and 34% at week 2. After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced. To our knowledge, this is the first study that demonstrates that substituting tobacco cigarettes with an e-cigarette may reduce user exposure to numerous toxicants and carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to harmful constituents that are present in tobacco cigarettes and e-cigarettes can aid in evaluating e-cigarettes as a potential harm reduction device.

Vapours of US and EU Market Leader Electronic Cigarette Brands and Liquids Are Cytotoxic for Human Vascular Endothelial Cells.

The present study was conducted to provide toxicological data on e-cigarette vapours of different e-cigarette brands and liquids from systems viewed as leaders in the e-cigarette market and to compare e-cigarette vapour toxicity to the toxicity of conventional strong high-nicotine cigarette smoke. Using an adapted version of a previously constructed cigarette smoke constituent sampling device, we collected the hydrophilic fraction of e-cigarette vapour and exposed human umbilical vein endothelial cells (HUVECs) to the mixture of compounds present in the vapour of 4 different single-use e-cigarettes, 6 different liquid vapours produced by the same refillable e-cigarette, and one e-cigarette with an exchangeable liquid cartridge. After incubation of cells with various concentrations and for various periods of time we analysed cell death induction, proliferation rates, the occurrence of intra-cellular reactive oxygen species, cell morphology, and we also measured e-cigarette heating coil temperatures. Overall, conventional cigarette smoke extract showed the most severe impact on endothelial cells. However, some e-cigarette vapour extracts showed high cytotoxicity, inhibition of cell proliferation, and alterations in cell morphology, which were comparable to conventional high-nicotine cigarettes. The vapours generated from different liquids using the same e-cigarette show substantial differences, pointing to the liquids as an important source for toxicity. E-cigarette vapour-mediated induction of oxidative stress was significant in one out of the 11 analysed vapours. There is a high variability in the acute cytotoxicity of e-cigarette vapours depending on the liquid and on the e-cigarettes used. Some products showed toxic effects close to a conventional high-nicotine cigarette. Liquid nicotine, menthol content, and the formation of acute intracellular reactive oxygen species do not seem to be the central elements in e-cigarette vapour toxicity.

Novel long chain fatty acid derivatives of quercetin-3-O-glucoside reduce cytotoxicity induced by cigarette smoke toxicants in human fetal lung fibroblasts

Smoking has become a global health concern due to its association with many disease conditions, such as chronic obstructive pulmonary disease (COPD), cardiovascular diseases (CVD) and cancer. Flavonoids are plant polyphenolic compounds, studied extensively for their antioxidant, anti-inflammatory, and anti-carcinogenic properties. Quercetin-3-O-glucoside (Q3G) is a flavonoid which is widely found in plants. Six novel long chain fatty acid [stearic acid, oleic acid, linoleic acid, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] derivatives of Q3G were evaluated for their potential in protecting human lung fibroblasts against cytotoxicity induced by selected cigarette smoke toxicants: 4-(methylnitrosoamino)-1-(3-pyridinyl)-1-butanone (NNK), benzo-α-pyrene (BaP), nicotine and chromium (Cr[VI]). Nicotine and Cr[VI] induced toxicity in fibroblasts and reduced the percentage of viable cells, while BaP and NNK did not affect cell viability. The fatty acid derivatives of Q3G provided protection against nicotine- and Cr[VI]-induced cell death and membrane lipid peroxidation. Based on the evaluation of inflammatory markers of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2), the fatty acid derivatives of Q3G were found to be effective in lowering the inflammatory response. Overall, these novel fatty acid esters of Q3G warrant further investigation as potential cytoprotective agents.

Intracellular Metabolism of α,β-Unsaturated Carbonyl Compounds, Acrolein, Crotonaldehyde and Methyl Vinyl Ketone, Active Toxicants in Cigarette Smoke: Participation of Glutathione Conjugation Ability and Aldehyde-Ketone Sensitive Reductase Activity.

The major toxicants in cigarette smoke, α,β-unsaturated aldehydes, such as acrolein (ACR) and crotonaldehyde (CA), and α,β-unsaturated ketone, methyl vinyl ketone (MVK), are known to form Michael-type adducts with glutathione (GSH) and consequently cause intracellular GSH depletion, which is involved in cigarette smoke-induced cytotoxicity. We have previously clarified that exposure to cigarette smoke extract (CSE) of a mouse melanoma cell culture medium causes rapid reduction of intracellular GSH levels, and that the GSH-MVK adduct can be detected by LC/MS analysis while the GSH-CA adduct is hardly detected. In the present study, to clarify why the GSH-CA adduct is difficult to detect in the cell medium, we conducted detailed investigation of the structures of the reaction products of ACR, CA, MVK and CSE in the GSH solution or the cell culture medium. The mass spectra indicated that in the presence of the cells, the GSH-CA and GSH-ACR adducts were almost not detected while their corresponding alcohols were detected. On the other hand, both the GSH-MVK adducts and their reduced products were detected. In the absence of the cells, the reaction of GSH with all α,β-unsaturated carbonyls produced only their corresponding adducts. These results show that the GSH adducts of α,β-unsaturated aldehydes, CA and ACR, are quickly reduced by certain intracellular carbonyl reductase(s) and excreted from the cells, unlike the GSH adduct of α,β-unsaturated ketone, MVK. Such a difference in reactivity to the carbonyl reductase might be related to differences in the cytotoxicity of α,β-unsaturated aldehydes and ketones.

Mass Spectrometric Approaches to the Identification of Potential Ingredients in Cigarette Smoke Causing Cytotoxicity.

Cigarette smoke contains many harmful chemicals that contribute to the pathogenesis of smoking-related diseases such as chronic obstructive pulmonary disease, cancer, and cardiovascular disease. Many studies have been done to identify cytotoxic chemicals in cigarette smoke and elucidate the onset of the above-mentioned diseases caused by smoking. However, definitive mechanisms for cigarette smoke toxicity remain unknown. As candidates for cytotoxic chemicals, we have recently found methyl vinyl ketone (MVK) and acetic anhydride in nicotine/tar-free cigarette smoke extract (CSE) using L-tyrosine (Tyr), an amino acid with highly reactive hydroxyl group. The presence of MVK and acetic anhydride in CSE was confirmed by gas chromatography-mass spectrometry (GC/MS). We also found new reaction products formed in B16-BL6 mouse melanoma (B16-BL6) cells treated with CSE using LC/MS. These were identified as glutathione (GSH) conjugates of α,β-unsaturated carbonyl compounds, MVK, crotonaldehyde (CA), and acrolein (ACR), by the mass value and product ion spectra of these new products. ACR and MVK are type-2 alkenes, which are well known as electron acceptors and form Michael-type adducts to nucleophilic side chain of amino acids on peptides. These α,β-unsaturated carbonyl compounds may have a key role in CSE-induced cell death.

A comparative assessment of cigarette smoke aerosols using an in vitro air–liquid interface cytotoxicity test

This study describes the evaluation of a modified air-liquid interface BALB/c 3T3 cytotoxicity method for the assessment of smoke aerosols in vitro. The functionality and applicability of this modified protocol was assessed by comparing the cytotoxicity profiles from eight different cigarettes. Three reference cigarettes, 1R5F, 3R4F and CORESTA Monitor 7 were used to put the data into perspective and five bespoke experimental products were manufactured, ensuring a balanced and controlled study. Manufactured cigarettes were matched for key variables such as nicotine delivery, puff number, pressure drop, ventilation, carbon monoxide, nicotine free dry particulate matter and blend, but significantly modified for vapor phase delivery, via the addition of two different types and quantities of adsorptive carbon. Specifically manufacturing products ensures comparisons can be made in a consistent manner and allows the research to ask targeted questions, without confounding product variables. The results demonstrate vapor-phase associated cytotoxic effects and clear differences between the products tested and their cytotoxic profiles. This study has further characterized the in vitro vapor phase biological response relationship and confirmed that the biological response is directly proportional to the amount of available vapor phase toxicants in cigarette smoke, when using a Vitrocell® VC 10 exposure system. This study further supports and strengthens the use of aerosol based exposure options for the appropriate analysis of cigarette smoke induced responses in vitro and may be especially beneficial when comparing aerosols generated from alternative tobacco aerosol products.

Teratogenic, bioenergetic, and behavioral effects of exposure to total particulate matter on early development of zebrafish (Danio rerio) are not mimicked by nicotine

Cigarette smoke has been associated with a number of pathologies; however, the mechanisms leading to developmental effects are yet to be fully understood. The zebrafish embryo is regarded as a ‘bridge model’; however, not many studies examined its applicability to cigarette smoke toxicity. This study examined the effects of total particulate matter (TPM) from 3R4F reference cigarettes on the early development of zebrafish (Danio rerio). Zebrafish embryos were exposed to two concentrations of TPM (0.4 and 1.4μg/mL equi-nicotine units) or nicotine at equivalent doses. The exposures began at 2h post-fertilization (hpf) and lasted until 96hpf. Several physiological parameters were assessed during or after the exposure. We show that TPM increased mortality, delayed hatching, and increased the incidence of deformities in zebrafish. TPM exposure also increased the incidence of hemorrhage and disrupted the angiogenesis of the major vessels in the brain. Moreover, TPM exposure reduced the larval body length, decreased the heart rate, and reduced the metabolic rate. Biomarkers of xenobiotic metabolism and oxidative stress were also affected. TPM-exposed zebrafish also differed behaviorally: at 24hpf the embryos had a higher frequency of spontaneous contractions and at 144hpf the larvae displayed swimming hyperactivity. This study demonstrates that TPM disrupts several aspects of early development in zebrafish. The effects reported for TPM were not attributable to nicotine, since embryos treated with nicotine alone did not differ significantly from the control group. Collectively, our work illustrates the utility of zebrafish as an alternative model to evaluate the toxic effects of cigarette smoke constituents.

Protection of coronary endothelial cells from cigarette smoke-induced oxidative stress by a new MnII-containing polyamine-polycarboxilate scavenger of superoxide anion

Oxidative stress plays a major role in cardiovascular injury and dysfunction induced by cigarette smoke. Smoke-borne pro-oxidants impair endothelial function and predispose to thrombosis, inflammation and atherosclerosis. This in vitro study evaluates whether MnII(4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate).2H2O (MnII(Me2DO2A)), a polyamine–polycarboxilate, MnII-containing O2− scavenger, has a direct protective action on guinea pig coronary endothelial (GPCE) cells exposed to cigarette smoke extracts (CSE).MnII(Me2DO2A) (1–10μmol/l) was added to the culture medium together with CSE and maintained for 4h. In parallel experiments, the inactive congener ZnII(Me2DO2A), in which ZnII replaced the functional MnII center in the same organic scaffold, was used as negative control.MnII(Me2DO2A), mostly at the higher doses (5 and 10μmol/l), significantly increased GPCE cell viability (trypan blue assay), improved mitochondrial activity (MTT test, mitochondrial membrane potential Δψ), reduced cellular apoptosis (mPTP, caspase-3 activity, TUNEL assay), decreased intracellular ROS levels (H2DCFDA), lipoperoxidation (BODIPY 581/591) and decreased protein nitrosylation. Of note, ZnII(Me2DO2A) did not preserve cell viability. These findings suggest that MnII(Me2DO2A) is a promising O2− scavenging compound able to protect from cigarette smoke-induced oxidative cell injury. In perspective, should its efficacy be confirmed in future in vivo studies, this molecule might represent a therapeutic or preventive drug to counteract cigarette smoke toxicity.

Empirical characterisation of ranges of mainstream smoke toxicant yields from contemporary cigarette products using quantile regression methodology

Approximately 100 toxicants have been identified in cigarette smoke, to which exposure has been linked to a range of serious diseases in smokers. Smoking machines have been used to quantify toxicant emissions from cigarettes for regulatory reporting. The World Health Organization Study Group on Tobacco Product Regulation has proposed a regulatory scenario to identify median values for toxicants found in commercially available products, which could be used to set mandated limits on smoke emissions. We present an alternative approach, which used quantile regression to estimate reference percentiles to help contextualise the toxicant yields of commercially available products with respect to a reference analyte, such as tar or nicotine. To illustrate this approach we examined four toxicants (acetone, N′-nitrosoanatabine, phenol and pyridine) with respect to tar, and explored International Organization for Standardization (ISO) and Health Canada Intense (HCI) regimes. We compared this approach with other methods for assessing toxicants in cigarette smoke, such as ratios to nicotine or tar, and linear regression. We concluded that the quantile regression approach effectively represented data distributions across toxicants for both ISO and HCI regimes. This method provides robust, transparent and intuitive percentile estimates in relation to any desired reference value within the data space.

Variation in tobacco and mainstream smoke toxicant yields from selected commercial cigarette products.

There is a drive toward the mandated lowering and reporting of selected toxicants in tobacco smoke. Several studies have quantified the mainstream cigarette emissions of toxicants, providing benchmark levels. Few, however, have examined how measured toxicant levels within a single product vary over time due to natural variation in the tobacco, manufacturing and measurement. In a single centre analysis, key toxicants were measured in the tobacco blend and smoke of 3R4F reference cigarette and three commercial products, each sampled monthly for 10 months. For most analytes, monthly variation was low (coefficient of variation <15%); but higher (⩾ 20%) for some compounds present at low (ppb) levels. Reporting toxicant emissions as a ratio to nicotine increased the monthly variation of the 9 analytes proposed for mandated lowering, by 1-2 percentage points. Variation in toxicant levels was generally 1.5-1.7-fold higher in commercial cigarettes compared with 3R4F over the 10-month period, but increased up to 3.5-fold for analytes measured at ppb level. The potential error (2CV) associated with single-point-in-time sampling averaged ∼ 20%. Together, these data demonstrate that measurement of emissions from commercial cigarettes is associated with considerable variation for low-level toxicants. This variation would increase if the analyses were conducted in more than one laboratory.

Crosstalk Between Co-cultured A549 Cells and THP1 Cells Exposed to Cigarette Smoke.

Cigarette smoke (CS) is considered as a major etiological factor in the pathogenesis of chronic obstructive pulmonary disease. In this study we used A549 cells and THP-1 cells grown for 24 h in monoculture or in co-culture in CS-conditioned media and changes in their proliferation, viability, acetylated histone H3 levels and expression of extracellular antigens CD14, HLA-DR, CD11a, and CD11b were assessed. CS was highly toxic to A549 cells but not to THP1 cells. In A549 cells, oxidative stress reached the highest values after 1 h of CS exposure and then decreased. In THP1 cells oxidative stress was lower and increased progressively with time. CS decreased proliferation of A549 and THP1 cells by about 80% and 21%, respectively. CS did not alter acetylated histone H3 levels in A549 cells, while in THP1 cells the levels were reduced by about 35%. CS significantly increased expression of CD14, HLA-DR, CD11a, and CD11b in THP1 cells. In co-culture, naïve or CS-pretreated THP1 cells significantly protected A549 cells against CS toxicity but had higher death rates. These results show that epithelial cells are more fragile to CS than monocytes and that CS-activated monocytes may protect epithelial cells against CS-induced cytotoxicity.

Approaches for the design of reduced toxicant emission cigarettes.

Cigarette smoking causes serious diseases through frequent and prolonged exposure to toxicants. Technologies are being developed to reduce smokers’ toxicant exposure, including filter adsorbents, tobacco treatments and substitutes. This study examined the effect of modifications to filter ventilation, variations in cigarette circumference and active charcoal filter length and loading, as well as combinations of these features in a reduced-toxicant prototype (RTP) cigarette, on the yields of toxicants in cigarette smoke. An air-dilution mechanism, called split-tipping, was developed in which a band of porous paper in the centre of the filter tipping functions to minimise the loss of effective filter ventilation that occurs at the high flow rates encountered during human-smoking, and to facilitate the diffusional loss of volatile toxicants. As compared with conventional filter ventilation cigarettes, split-tipping reduced tar and volatile smoke constituent emissions under high flow rate machine-smoking conditions, most notably for products with a 1-mg ISO tar yield. Furthermore, mouth level exposure (MLE) to tar and nicotine was reduced among smokers of 1-mg ISO tar cigarettes in comparison to smokers of cigarettes with traditional filter ventilation. For higher ISO tar level cigarettes, however, there were no significant reductions in MLE. Smaller cigarette circumferences reduced sidestream toxicant yields and modified the balance of mainstream smoke chemistry with reduced levels of aromatic amines and benzo[a]pyrene but increased yields of formaldehyde. Smaller circumference cigarettes also had lower mainstream yields of volatile toxicants. Longer cigarette filters containing increased levels of high-activity carbon (HAC) showed reduced machine-smoking yields of volatile toxicants: with up to 97% removal for some volatile toxicants at higher HAC loadings. Split-tipping was combined with optimal filter length and cigarette circumference in an RTP cigarette that gave significantly lower mainstream (up to ~90%) and sidestream (predominately 20%–60%) smoke yields of numerous toxicants as compared with a commercial comparator cigarette under machine-smoking conditions. Significantly lower mainstream and sidestream smoke toxicant yields were observed for an RTP cigarette comprising several toxicant reducing technologies; these observations warrant further evaluation in clinical studies where real-world relevance can be tested using biomarkers of exposure and physiological effect.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-374) contains supplementary material, which is available to authorized users.

Science, policy and the rise of ‘thirdhand smoke’ as a public health issue

‘Thirdhand smoke’, the designated term for the cigarette smoke toxicants that linger on room and car surfaces long after the smoke itself dissipates, is a concept that has gained increasing prominence in tobacco control policy and research over the past six years. In this paper, I track the emergence of thirdhand smoke as a social and scientific concept, conducting a critical analysis of newspaper reports and references to the term in the academic and policy literature. Demonstrating that claims about the health effects of thirdhand smoke occurred in the absence of evidence of harm, I examine the broader sociopolitical conditions that enabled the concept to become meaningful (and useful). I show that some of the concept’s legitimacy came from its presentation as a natural extension of secondhand smoke, and its framing as a particular threat to babies and children. However, I argue that the experiential, embodied dimension of thirdhand smoke itself was crucial to its success.

A comprehensive evaluation of the toxicology of different cut widths of tobacco in experimental cigarettes

Context: Literature suggests that the width of tobacco strips in cigarettes may affect the smoke chemistry and toxicology of such products.Objective: A comprehensive analysis of smoke from experimental cigarettes can be used to determine whether different cut widths of tobacco result in different toxicological activity.Materials and methods: A battery of tests was used to compare the chemistry and in vitro and in vivo toxicology of smoke from experimental cigarettes made with tobacco cut to different widths.Results: Different cut widths of tobacco did not elicit consistent and significant differences in cigarette smoke chemistry, responses in in vitro mutagenicity or cytotoxicity assays or most endpoints in 90-d rat inhalation studies. Of note, however, were atypical in-life observations and slightly depressed body weights observed in two rat inhalation studies.Conclusion: Most of our data indicate that different cut widths of tobacco used in cigarettes are unlikely to change the toxicity of mainstream cigarette smoke; however, without additional investigation, the atypical in-life observations and depression in body weights cast doubt on the toxicological acceptability of cutting the tobacco into wider shreds.