Toxins In Cigarette Smoke Research Articles

Quality variations of leachate resulting from cigarette filter recycling as a challenge for its management

Recycling is known as a solution for cigarette filter management, but this may cause the release of trapped pollutants in it. Cigarette smoke toxins and chemicals that trapped in the cigarette filter can accumulate in the recycling leachate. In this study, littered cigarette filters and freshly smoked cigarette filters were recycled and the resulting leachate was analyzed. The results showed that the minimum and maximum Chemical Oxygen Demand (COD) of the studied leachates were 2100 mg/L and 11,300 mg/L, respectively. The maximum temporal variation in the studied leachate quality was 74.28%, but the maximum spatial variation was 314.2%. COD in the freshly smoked sample was 2600–9200 mg/L more than the littered samples. The average concentration of chromium, lead, nickel, and cadmium in littered samples was 0.023, 0.024, 0.045, and 0.019 mg/L, respectively. Environmental conditions such as humidity, the efficiency of the urban cleaning system in reducing the resistance of littered filters, the difference in the quality of the filter and tobacco, and the difference in smoking behaviors were effective in this variation. Reducing the toxicity of cigarette smoke and improving the efficiency of the urban cleaning system can lead to the same quality, but leachate treatment is necessary to reduce the environmental risk.

Expression of Concern: Cigarette Smoke Toxins Deposited on Surfaces: Implications for Human Health.

Expression of Concern: Cigarette Smoke Toxins Deposited on Surfaces: Implications for Human Health.

High Counts and Anthracene Degradation Ability of Streptococcus mutans and Veillonella parvula Isolated From the Oral Cavity of Cigarette Smokers and Non-smokers.

The composition and metabolic functions of oral microbiota are affected by many factors including smoking leading to several health problems. Cigarette smoking is associated with changes in oral microbiota composition and function. However, it is not known if the depletion of certain bacterial genera and species is due to specific toxins in cigarette smoke, or indirectly due to competition for colonization with smoking-enriched bacteria. Therefore, the aim of this study was to determine the effect of cigarette smoking on the microbial prevalence and polycyclic aromatic hydrocarbons (PAHs) biodegradation of selected enriched and depleted oral bacteria from oral microbiota of smokers compared to that in non-smokers. Samples of oral rinse from smokers and non-smokers were collected (n = 23, 12 smokers and 11 non-smokers) and screened for oral bacterial strains of Streptococcus mutans, Lactobacillus spp., and Veillonella spp. Comparing counts, S. mutans, V. tobetsuensis, and V. dispar showed higher counts in smokers compared to non-smokers while the Lactobacillus spp. were higher in non-smokers. Lactobacillus fermentum was prevalent in smokers, representing 91.67% of the total Lactobacillus spp. isolates. The biodegradation potential of anthracene; a representative of PAHs of collected isolates, in single and mixed cultures, was assayed with anthracene as the sole source of carbon using 2,6-dichlorophenol indophenol (2,6-DCPIP) as indicator. S. mutans isolates recovered from smokers showed higher degradation of anthracene compared to those recovered from non-smokers. The anaerobic anthracene biodegradation activity of V. parvula isolates from non-smokers was the highest among all isolates of the three recovered genera from the same subject. The anthracene biodegradation potential of Lactobacillus spp. was variable. Combinations of isolated bacteria in co-cultures showed that Lactobacillus spp. interfered with anthracene biodegradation ability along with the viable counts of S. mutans and Veillonella spp. In conclusion, oral dysbiosis due to cigarette smoking was observed not only due to changes in oral bacterial relative abundance but also extended to bacterial functions such as anthracene biodegradation tested in this study. Microbe–microbe interactions changed the anthracene biodegradation potential and growth of the microbial mixture compared to their corresponding single isolates, and these changes differ according to the constituting bacteria.

Knowledge and Awareness of Added Sugar in Cigarettes.

Sugars naturally occur in tobacco leaf but are also commonly added to cigarettes by tobacco companies. Added sugar increases levels of toxic chemicals in cigarette smoke. Little is known about smokers' knowledge of added sugar in cigarettes and awareness of its effects. Adult cigarette smokers were recruited through Amazon Mechanical Turk to participate in an online experiment on electronic cigarette advertising. After completing the experiment, participants (N = 4351) answered two items assessing knowledge and awareness of added sugar in cigarettes. Participants had the option of providing open-ended comments about the overall study, and two reviewers read and independently coded comments pertaining to the sugar items. Only 5.5% of participants responded "yes" to the question: "Is sugar added to cigarettes?", and only 3.8% of participants indicated being aware that added sugar increases toxins in cigarette smoke. Forty-eight participants mentioned the sugar items when asked to comment about the overall questionnaire. Fifty-two percent of these comments expressed an interest in obtaining more information about added sugar, and 23% described the sugar items as interesting or informative. Three participants commented that learning about added sugar motivated them to quit or cut down on smoking. Among a large sample of smokers, few reported knowledge of added sugar in cigarettes and awareness of its effects. Further, several smokers expressed an interest in learning more about added sugar. Messages about added sugar in cigarettes may be a promising new angle for campaigns to discourage smoking. Few American smokers are aware that sugar is added to cigarettes, and some participants expressed a desire to learn more about this additive. Given such low awareness, the interest among smokers, and increased popular concerns about added sugar in foods and beverages, messaging about added sugar in cigarettes should be developed and tested for inclusion in public health media campaigns.

Abstract 1433: Single cell RNA sequencing reveals smoking-associated alterations in bronchial airway epithelial subpopulations

Abstract Rationale: We have previously shown that bronchial airway epithelial gene expression reflects the physiologic response to cigarette smoke exposure. We have also shown that gene expression differences in cytologically normal airways cells can serve as a diagnostic biomarker for lung cancer. In this study, we use single cell RNA-seq to profile transcriptomes of individual bronchial epithelial cells from current and never smokers in order to detect smoking-associated alterations within specific epithelial cell types and to discover novel subpopulations that develop as a result of smoke exposure. This approach may be useful for identifying cell type-specific transcriptomic changes in the airways of cancer patients, which may lead to a better understanding of lung carcinogenesis and new approaches to early lung cancer detection. Methods: We obtained bronchial brushings from current smokers (n=6) and never smokers (n=6) and isolated single cells by FACS. The CEL-Seq RNA library preparation protocol was used to sequence the transcriptomes of 1,140 cells (n=95/donor). Results: Distinct populations of bronchial cells expressed known markers of basal (KRT5), ciliated (FOXJ1), secretory (SCGB1A1, MUC5AC) epithelial cells, as well as white blood cells (CD45). In the airways of smokers, we observed an increase in abundance of MUC5AC+ secretory cells as well as a decrease in abundance of KRT5+ basal cells and SCGB1A1+ secretory cells. A novel subset of KRT8+ cells that lacked expression of other known cell type markers was identified in the airways of smokers and may represent a population previously described as undifferentiated intermediate cells. Genes involved with metabolism of polycyclic aromatic hydrocarbons (CYP1B1) were detected in smoker secretory cells, whereas genes involved in the metabolic response to cigarette smoke toxins such as aldehydes (ALDH3A1) and quinones (NQO1), were most highly expressed by smoker ciliated cells. Interestingly, the novel KRT8+ cells identified in smokers expressed genes known to promote MUC5AC+ secretory cell differentiation (SPDEF), but did not express MUC5AC itself, suggesting that these may be pro-MUC5AC+ secretory intermediate cells. Furthermore, we found that genes previously associated with higher expression in the airways of lung cancer patients were enriched among genes most strongly associated with smoker ciliated and secretory cells, whereas genes with lower expression in lung cancer were enriched among genes most strongly associated with white blood cells. Conclusion: We have identified cell type-specific transcriptomic alterations and shifts in epithelial cell population abundance in smoker airways. In future studies, profiling the transcriptomes of single cells from bronchial airways of smokers with and without lung cancer may lead to the identification of specific cellular subpopulations contributing to the airway field of lung-cancer associated injury. Citation Format: Grant E. Duclos, Joshua D. Campbell, Yaron Gesthalter, Patrick Autissier, Yves M. Dumas, Robert Terrano, Gang Liu, Marc E. Lenburg, Avrum Spira, Jennifer Beane. Single cell RNA sequencing reveals smoking-associated alterations in bronchial airway epithelial subpopulations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1433. doi:10.1158/1538-7445.AM2017-1433

Dichotomous effects of aryl hydrocarbon receptor (AHR) activation on human fetoplacental endothelial cell function

IntroductionMaternal cigarette smoking is associated with elevated fetoplacental vascular resistance and fetal growth restriction (FGR). While studies have demonstrated varying effects of nicotine on blood flow, the role of polycyclic aromatic hydrocarbons (PAHs), abundant toxins in cigarette smoke that cross the placenta, has not been elucidated. We hypothesized that exposure of human fetoplacental endothelial cells (ECs) to the PAH benzo[a]yrene (BaP) would result in up-regulation of cyclooxygenase-2 (PTGS2) and preferential production of vasoconstrictive prostanoids via activation of the aryl hydrocarbon receptor (AHR) pathway. MethodsECs were isolated, cultured, and treated with vehicle or BaP. ECs were subjected to real-time PCR, western blotting, enzyme immunoassays, wound scratch assays, tube formation assays, and RNA interference against AHR. Statistical analyses were performed with Student’s t-test, one-way ANOVA followed by multiple comparisons testing when appropriate, or the Kruskal-Wallis H test. ResultsBaP induced PTGS2 expression (p < 0.05) and production of the stable metabolite of prostacyclin (p = 0.001) in fetoplacental ECs without affecting thromboxane. These effects were ablated by PTGS2 inhibition (p < 0.01) and RNA interference of AHR (p < 0.001). Surprisingly, despite the induction of prostacyclin, EC migration (p = 0.007) and tube formation (p = 0.003) were inhibited by BaP. AHR inhibition, however, rescued tube formation (p = 0.008). DiscussionBaP-mediated AHR activation results in induction of PTGS2 expression and enhanced production of prostacyclin metabolite. Despite an increase in this vasodilatory and pro-angiogenic prostanoid, BaP exposure also impairs EC migration and angiogenesis through AHR. This suggests that PAH may adversely affect the fetoplacental vasculature through its regulation of angiogenesis.

Metabolomics reveals metabolic changes in male reproductive cells exposed to thirdhand smoke

Thirdhand smoke (THS) is a new term for the toxins in cigarette smoke that linger in the environment long after the cigarettes are extinguished. The effects of THS exposure on male reproduction have not yet been studied. In this study, metabolic changes in male germ cell lines (GC-2 and TM-4) were analyzed after THS treatment for 24 h. THS-loaded chromatography paper samples were generated in a laboratory chamber system and extracted in DMEM. At a paper: DMEM ratio of 50 μg/ml, cell viability in both cell lines was normal, as measured by the MTT assay and markers of cytotoxicity, cell cycle, apoptosis and ROS production were normal as measured by quantitative immunofluorescence. Metabolomic analysis was performed on methanol extracts of GC-2 and TM-4 cells. Glutathione metabolism in GC-2 cells, and nucleic acid and ammonia metabolism in TM-4 cells, was changed significantly by THS treatment. RT-PCR analyses of mRNA for enzyme genes Gss and Ggt in GC-2 cells, and TK, SMS and Glna in TM-4 cells reinforced these findings, showing changes in the levels of enzymes involved in the relevant pathways. In conclusion, exposure to THS at very low concentrations caused distinct metabolic changes in two different types of male reproductive cell lines.

Punicalagin improves chorioallantoic and yolk sac vasculogenesis and teratogenesis of embryos induced by nicotine exposure

Punicalagin is a functional ingredient in pomegranate juice, which has various beneficial effects for health and prevention of disease. In this study, the anti-teratogenic effect of punicalagin (1 × 10−5 or 1 × 10−4 µM) was investigated in cultured mouse embryos and yolk sac-placentas exposed to nicotine (1 mM), one of the main toxins in cigarette smoke. Nicotine-treated embryos revealed severe anomalies as well as impaired yolk sac vascularization, reduced labyrinth formation, and developmental arrest of blood islands in the chorioallantoic border. Furthermore, nicotine significantly altered the regulations of hypoxia- and vascularization-related genes in yolk sac-placenta and the levels of oxidative stress, apoptosis, and inflammation in both embryos and yolk sac-placentas. However, these detrimental changes were remarkably improved in response to co-treatment with punicalagins. These findings indicate that punicalagin could be crucial to the development of clinical strategies to attenuate nicotine-induced teratogenesis in embryos.

Dioxin Exposure Impairs BMP-2-Mediated Spinal Fusion in a Rat Arthrodesis Model.

Cigarette smoking inhibits bone-healing and leads to increased rates of pseudarthrosis. However, the mechanisms behind these effects are controversial. Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin)--a cigarette smoke constituent and potent activator of the aryl hydrocarbon receptor (Ahr)--negatively impacts bone quality and osteoblast differentiation. We hypothesized that activation of the Ahr by dioxin would inhibit bone morphogenetic protein (BMP)-2-mediated spinal fusion in a rat arthrodesis model. Female Long-Evans rats were pretreated with dioxin or vehicle in six weekly doses, followed by bilateral posterior lumbar spinal fusion across the L4-L5 transverse processes using recombinant human BMP (rhBMP)-2. Treatments continued until sacrifice at four weeks postoperatively. A third group was treated with dioxin for six weeks, followed by a recovery period of four elimination half-lives to assess the reversible effects of dioxin exposure on spinal fusion capacity. Bone formation and fusion capacity were evaluated using fusion scoring, radiography, micro-computed tomography, and histologic analysis. Fusion scores for dioxin-treated and dioxin-recovery rats were significantly lower than those for controls. Although fusion rates were also significantly reduced in dioxin-treated animals relative to controls (50% versus 100%, respectively), rates were not significantly reduced in dioxin-recovery animals (80%). Dioxin treatment significantly inhibited spinal fusion in a rat arthrodesis model, and a prolonged cessation of dioxin exposure facilitated only a partial recovery of bone-healing capacity. This finding indicates that, although the effects of dioxin are persistent, an extended recovery from exposure could potentially restore bone regeneration in vivo. Development of a pharmacologic agent that reduces the adverse effects of cigarette smoke on bone-healing could prove useful to orthopaedic surgeons. Since dioxin and other similar cigarette smoke toxins exert their effects through Ahr pathway activation, the receptor represents a potential therapeutic target to improve spinal fusion rates in patients who smoke.

How smoking during pregnancy affects the mother and fetus

The prevalence of smoking during pregnancy remains unacceptably high. There are serious adverse effects on both the mother and fetus; various toxins in cigarette smoke contribute to placental changes, reduced blood flow, leading to inadequate nutrient availability and tissue necrosis. Complications include reduced fetal growth, shortened gestation and an increased risk of congenital abnormalities and stillbirth. All women who smoke during pregnancy should be biochemically identified, counselled on these adverse effects, and guided towards all available sources of help and advice, including smoking cessation services and pharmacies.

Tobacco Control Policies and Their Impacts. Past, Present, and Future

The 1964 Surgeon General's report on smoking and health concluded that "Cigarette smoking is a health hazard of sufficient importance in the United States to warrant appropriate remedial action." The adoption of remedial actions over the next half century produced what is arguably the most important public health triumph of that period in the United States and in other developed nations. At the heart of the remedial actions were governmental policies. By raising cigarette price, taxation is especially effective at reducing smoking, encouraging some smokers to quit and others to reduce their daily consumption, while also discouraging the initiation of smoking by children. Smoke-free workplace policies have dramatically reduced workers' exposure to the toxins in cigarette smoke, smoking, employers' costs, and the incidence of acute myocardial infarctions. Other policies have also helped diminish the toll of smoking. The successes of tobacco control notwithstanding, future progress will occur slowly unless society finds new, possibly radical "endgame" strategies to hasten the arrival of a smoke-free society.

Cigarette smoke toxins deposited on surfaces: implications for human health.

Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS) is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered – Thirdhand smoke (THS) – the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker) similar to those found in children exposed to SHS (and consequently to THS). In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.

Effects of Genes and Environment on the Fetoplacental Arterial Microcirculation in Mice Revealed by Micro‐Computed Tomography Imaging

The fetoplacental arterial tree is critical for efficient distribution of arterial blood to capillaries throughout the placental exchange region; yet, little is known about the factors and mechanisms that control its development. Advances in micro-CT imaging and analysis, and available mutant mouse strains, are facilitating rapid progress. Indeed, micro-CT studies show that genetic differences between the CD1 and C57Bl/6 mouse strains, and between Gcm1 heterozygotes and wild-type littermates alter the developmental trajectory of the fetoplacental arterial tree as do environmental factors including maternal exposure to toxins in cigarette smoke and malarial infection. Relative to other vascular beds, the fetoplacental arterial tree is particularly tractable because veins can more easily be excluded when infusing the contrast agent and because of the placenta's small size, which means that the whole organ can be imaged (maintaining connectivity) and that the tree is simpler (fewer branching generations). Despite these differences, measured parameters were found to be similar to arterial trees in other adult rodent organs. Thus, micro-CT analysis provides a means for advancing of our understanding of the mechanisms controlling development of the fetoplacental arterial tree. Results will likely have relevance to other arterial vasculatures as well.

A ROUNDUP OF NEWS AND INFORMATION FROM OUR COMMUNITY

A ROUNDUP OF NEWS AND INFORMATION FROM OUR COMMUNITY

Adverse Effects of Cigarette Smoke and Induction of Oxidative Stress in Cardiomyocytes and Vascular Endothelium

Active and passive exposure to cigarette smoke (CS) increases the risk of, and has deleterious effects in, ischaemic heart disease. Exposure to CS increases infarct size in experimental models of coronary occlusion and reperfusion. Among many possible mechanisms for these deleterious effects in intact animals and humans three have more substantial evidence: 1) functional alterations of endothelial cells, neutrophils and platelets; 2) impaired mitochondrial function and energy metabolism caused by toxins in CS, including oxidative free radicals; 3) increased arterial stiffness and vulnerability of the atherosclerotic plaque. In addition to the various pro-mitogenic, carcinogenic and apoptotic pathways thought to be affected and upregulated by CS, a direct necrotic action on cardiomyocytes is also believed to exist. Many, if not all, of these alterations are caused by oxidative stress, either as a direct consequence of inhalation of free radicals, or by induction from the vast range of chemicals present in both the gas and solid phase of tobacco smoke. Here, some of the proposed mechanisms will be reviewed and their impact on the cardiomyocytes and peripheral vasculature discussed.

Estimating smokers' mouth-level exposure to select mainstream smoke constituents from discarded cigarette filter butts

Standardized machine smoking measurements are poor predictors of exposure. We have refined a method using the solanesol deposited in discarded cigarette butts as a marker for estimating deliveries of mainstream smoke constituents. Developing a fast and accurate method for measuring solanesol in cigarette filters to assess tobacco smoke intake could provide a way to assess how people smoke under natural conditions. We have developed and validated a new, lower-cost, high-throughput method to measure the solanesol content in discarded cigarette filter butts and correlated these measurements with mainstream smoke deliveries of nicotine and tobacco-specific nitrosamines (TSNAs). Cigarettes were machine smoked under a variety of conditions to cover a wide range of nicotine deliveries and solanesol levels in the spent cigarette filter. Following machine smoking, a 1-cm portion of filter material, measured from the mouth end, was removed from the cigarette butts for analysis. Although an isotopically labeled solanesol analog is currently not commercially available, we achieved excellent quantitative results using a structurally similar compound, geranylgeraniol, as an internal standard (IS). After spiking with IS and solvent extracted, solanesol extracts were then analyzed using liquid chromatography coupled with a single-quadrupole mass analyzer. Analysis was carried out using manual preparation as well as a high-throughput 48-well format using automated liquid handlers. Recoveries of solanesol from cigarette butts exceeded 95% with excellent precision and exhibited excellent linearity for both preparation methods. In addition, we show that the mouth-level exposure for both nicotine and TSNAs may be estimated by their relation to the solanesol retained in the cigarette filter. We believe that this method provides excellent versatility and throughput for the estimation of mouth-level exposure to a wide range of toxins in cigarette smoke under naturalistic conditions. In addition, this method allows a far more accurate measure of exposure both from a single cigarette as well as from daily smoking.

The place for harm reduction and product regulation in UK tobacco control policy

Tobacco use remains the leading cause of preventable death in this country and more needs to be done to reduce smoking rates. Harm reduction is one policy option. Smokers smoke for the nicotine, but die from the other toxins in cigarette smoke. Harm reduction in tobacco control aims to reduce the harm arising from nicotine use by shifting smokers, who are unable to quit, to using far less hazardous sources of nicotine, notably medicinal nicotine, in place of cigarettes. This article argues that for harm reduction to work in the UK, a nicotine product regulation authority is first needed. This would regulate nicotine products in proportion to harm to ensure that, contrary to the current paradoxical arrangements, the most harmful source of nicotine, the cigarette, becomes the most highly regulated (and thus the least easily accessible, available and attractive). It goes onto explore how a harm reduction strategy might be further developed, exploring controversies and potential pitfalls. It argues that the public health community needs to own and drive this debate because failure to do so would let the tobacco industry gain the upper hand and see thousands of more unnecessary deaths from tobacco use.

Smoking mentholated cigarettes impairs coronary microvascular function as severely as does smoking regular cigarettes

Objective — Smoking mentholated cigarettes inhibits the metabolism of nicotine and increases systemic exposure to cigarette smoke toxins. However, the possible effects of smoking mentholated cigarettes on coronary microvascular functions are unknown.We sought to investigate whether smoking mentholated cigarettes impairs coronary flow reserve (CFR) more so than smoking regular cigarettes.Methods — Twenty otherwise healthy smokers of regular cigarettes (6 women, 14 men; mean age, 25.6 ± 6.4 years) and 22 non-smoking control subjects were included in the study.To compare the acute effects of mentholated (0.9 mg nicotine, 11 mg tar, 12 mg carbon monoxide) and regular (0.9 mg nicotine, 12 mg tar, 12 mg carbon monoxide) cigarettes on CFR, all subjects underwent an echocardiographic examination that included CFR measurements at baseline. Twenty to 30 minutes after subjects had smoked 2 regular cigarettes and 2 mentholated cigarettes, CFR was again measured in subjects in the smoking group.Results — In response to smoking 2 regular and 2 mentholated cigarettes, CFR values declined from 2.56 ± 0.60 to 2.06 ± 0.38 (P < 0.004) and from 2.56 ± 0.60 to 2.14 ± 0.30 (P < 0.005), respectively. Smoking mentholated and regular cigarettes impaired CFR to the same degree (P =0.547).Conclusions — When compared with smoking regular cigarettes, smoking mentholated cigarettes has similar acute detrimental effects on coronary microvascular functions.

Effect of Delivered Dosage of Cigarette Smoke Toxins on the Levels of Urinary Biomarkers of Exposure

Urinary metabolites of tobacco smoke toxins are often used as biomarkers for the evaluation of active and passive exposure to cigarette smoke toxins. In a study of healthy smokers, we investigated concentrations of urinary biomarkers in relation to concentrations of selected toxins in mainstream cigarette smoke as determined by machine smoking of cigarettes in a manner that mimics an individual's smoking behavior (topography). Concentrations of nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and benzo(a)pyrene, in mainstream smoke determined under human smoking conditions, and their urinary metabolites cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, and 1-hydroxypyrene were established for 257 individuals who smoked low-yield (0.1-0.8 mg Federal Trade Commission nicotine/cigarette; mean, 0.66; n = 87), medium-yield (0.9-1.2 mg nicotine/cigarette; mean, 1.1; n = 109), and high-yield cigarettes (nicotine, >1.3 mg nicotine/cigarette; mean, 1.41; n = 61). Levels of urinary metabolites expressed per unit of delivered parent compounds decreased with increased smoke emissions. In smokers of low-, medium-, and high-yield cigarettes, the respective cotinine (ng/mg creatinine)-to-nicotine (mg/d) ratios were 89.4, 77.8, and 57.1 (low versus high; P = 0.06); the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (pmol/mg creatinine)-to-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (ng/d) ratios were 0.81, 0.55, and 0.57 (low versus high; P = 0.05); and the 1-hydroxypyrene (pg/mg creatinine)-to-benzo(a)pyrene (ng/d) ratios were 1.55, 1.13, and 0.97 (low versus high; P = 0.008). Similarly, means of cotinine per unit of delivered nicotine in smokers who consumed <20 cigarettes per day was 3.5-fold higher than in those who smoked >20 cigarettes per day. Likewise, a negative correlation was observed between cotinine-to-nicotine ratios and delivered doses of nicotine in subgroups of smokers who used the identical brand of cigarette, namely a filter tip-vented Marlboro (r = -0.59), which is a popular brand among Euro-Americans, and Newport (r = -0.37), a menthol-flavored cigarette without filter tip vents that is preferred by African-Americans. Thus, the intensity of the exposures significantly affects the levels of urinary biomarkers of exposure and should be taken into account in the evaluation of human exposure to cigarette smoke toxins.

Gender differences relative to smoking behavior and emissions of toxins from mainstream cigarette smoke

This study examined whether gender differences exist in the exposure to select mainstream cigarette smoke toxins as a result of differences in smoking behavior or type of cigarettes smoked among 129 female and 128 male smokers. Smoking topography data indicated that, compared with men, women took smaller puffs (37.6 ml/puff vs. 45.8 ml/puff; p = .0001) of shorter duration (1.33 s/puff vs. 1.48 s/puff; p = .002) but drew more puffs per cigarette (13.5 vs. 12.0; p = .001) and left longer butts (36.3 mm or 40.2% of cigarette length vs. 34.3 mm or 39.2% of cigarette length; p = .01). These trends were similar in both African Americans and European Americans. The emissions of select toxins per cigarette, as determined by mimicking human smoking behaviors were greater among the male smokers than the female smokers and correlated significantly with delivered smoke volume per cigarette. The geometric means of emissions of nicotine from cigarettes were 1.92 mg/cigarette (95% CI = 1.80-2.05) for women versus 2.20 (95% CI = 2.04-2.37) for men (p = .005). Cigarettes smoked by women yielded 139.5 ng/cigarette of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 95% CI = 128.8-151.0), compared with 170.3 ng/cigarette (95% CI = 156.3-185.6) for men (p = .0007); benzo(a)pyrene (BaP) emissions were 18.0 ng/cigarette (95% CI = 17.0-19.0) for women and 20.5 ng/cigarette (95% CI = 18.8-22.3) for men (p = .01). The gender differences with regard to cigarette smoke yields of toxins were more profound in European Americans than in African Americans. On average, African American men's smoking habits produced the highest emissions of select toxins from cigarettes, and European American female smokers had the lowest exposure to carcinogens and toxins. Several studies have suggested that women may be more susceptible than men to the ill effects of carcinogens in tobacco and tobacco smoke, whereas other studies have not found differences in lung cancer risk between men and women. The present study suggests that gender differences in exposure to tobacco smoke cannot account for a higher rate of lung cancer in female smokers compared with male smokers.