Cigarette Constituents Research Articles

Underreporting of non-study cigarette use by study participants confounds the interpretation of results from ambulatory clinical trial of reduced nicotine cigarettes

BackgroundAs part of its comprehensive plan to significantly reduce the harm from tobacco products, the US Food and Drug Administration is establishing a product standard to lower nicotine in conventional cigarettes to make them “minimally addictive or non-addictive". Many clinical studies have investigated the potential impact of such a standard on smoking behavior and exposure to cigarette constituents. These ambulatory studies required participants who smoke to switch to reduced nicotine study cigarettes. In contrast to clinical trials on pharmaceuticals or medical devices, participants had ready access to non-study conventional nicotine cigarettes and high rates of non-study cigarette use were consistently reported. The magnitude of non-compliance, which could impact the interpretation of the study results, was not adequately assessed in these trials.MethodsWe conducted a secondary analysis of data from a large, randomized trial of reduced nicotine cigarettes with 840 participants to estimate the magnitude of non-compliance, i.e., the average number of non-study cigarettes smoked per day by study participants assigned to reduced nicotine cigarettes. Individual participants’ non-study cigarette use was estimated based on his/her urinary total nicotine equivalent level, the nicotine content of the study cigarette assigned and the self-reported number of cigarettes smoked, using a previously published method.ResultsOur analysis showed that (1) there is a large variation in the number of non-study cigarettes smoked by participants within each group (coefficient of variation 90–232%); (2) participants in reduced nicotine cigarette groups underreported their mean number of non-study cigarettes smoked per day by 85–91%; and (3) the biochemical-based estimates indicate no reduction in the mean number of total cigarettes smoked per day for any group assigned to reduced nicotine cigarettes after accounting for non-study cigarettes.ConclusionsHigh levels of non-compliance, in both the rate and magnitude of non-study cigarette use, are common in ambulatory reduced nicotine cigarette trials where participants have access to conventional nicotine non-study cigarettes. The potential impact of high non-compliance on study outcomes should be considered when interpreting the results from such ambulatory studies.

A revision of the multiple-path particle dosimetry model focusing on tobacco product aerosol dynamics.

To assess the health impact of inhaled aerosols, it is necessary to understand aerosol dynamics and the associated dosimetry in the human respiratory tract. Although several studies have measured or simulated the dosimetry of aerosol constituents, the respiratory tract focus areas have been limited. In particular, the aerosols generated from tobacco products are complex composites and simulating their dynamics in the respiratory tract is challenging. To assess the dosimetry of the aerosol constituents of tobacco products, we developed a revised version of the Multiple-Path Particle Dosimetry (MPPD) model, which employs (1) new geometry based on CT-scanned human respiratory tract data, (2) convective mixing in the oral cavity and deep lung, and (3) constituent partitioning between the tissue and air, and clearance. The sensitivity analysis was conducted using aerosols composed of four major constituents of electronic cigarette (EC) aerosols to investigate the parameters that have a significant impact on the results. In addition, the revised model was run with 4 and 10 constituents in ECs and conventional cigarettes (CCs), respectively. Sensitivity analysis revealed that the new modeling and the physicochemical properties of constituents had a considerable impact on the simulated aerosol concentration and dosimetry. The simulations could be carried out within 3 min even when 10 constituents of CC aerosols were analyzed simultaneously. The revised model based on MPPD is an efficient and easy-to-use tool for understanding the aerosol dynamics of CC and EC constituents and their effect on the human body.

Influence of natural deep eutectic solvents on the release of volatile compounds from heated tobacco

Inspired by the emergence of natural deep eutectic solvents (DESs), we herein used thermogravimetry and pyrolysis-gas chromatography/mass spectrometry to probe the influence of six DESs (hydrogen bond acceptor=choline chloride, betaine, or l-proline; hydrogen bond donor=glycerol, 1,4-butanediol, or propylene glycol) on the release of volatiles from tobacco at 300 °C. DES treatment induced a 3.5–4.6% increase in second-stage weight loss and promoted the release of 28 aroma constituents (furans, aldehydes, ketones, and organic acids). Treatment with choline chloride-glycerol-propylene glycol increased the relative contents of the released 5-hydroxymethylfurfural and megastigmatrienone by factors of 1.2 and 3.6, respectively, whereas treatment with l-proline-glycerol promoted the release of 2,3-dihydro-3,5-dihydroxy-6-methyl-(4H)-pyran-4-one. Therefore, DES treatment facilitated the release of volatiles from tobacco powder and was inferred to be promising for the development of novel cigarette constituents.

‘If I hadn’t seen this picture, I'd be smoking’—perceptions about innovations in health warnings for cigarette packages in Brazil: a focus group study

ObjectiveTo investigate the perceptions of young people and adults, smokers and non-smokers about the current set of innovations introduced in 2018 into the Brazilian tobacco products’ health warnings.MethodsTwenty focus groups...

Effect of Cigarette Constituent Messages With Engagement Text on Intention to Quit Smoking Among Adults Who Smoke Cigarettes

The US Food and Drug Administration (FDA) is required to communicate the risks of tobacco constituents to the public. Few studies have addressed how FDA media campaigns can effectively communicate about cigarette smoke constituents. To examine whether messages about cigarette smoke constituents are effective in reducing smoking intentions and behaviors among adults who smoke. This randomized clinical trial enrolled participants who were aged between 18 and 65 years, were English speakers, were living in the United States, and who smoked at least 100 cigarettes during their lifetime and now smoked every day or some days. Participants received daily messages via email for 15 days. Participants were randomized to 1 of 2 message conditions or a control group and reported their previous-day smoking behaviors daily. Follow-up surveys were conducted on days 16 and 32. Data were collected from June 2017 to April 2018 and analyzed from April to September 2018. The 3 groups were (1) constituent plus engagement messages (eg, "Cigarette smoke contains arsenic. This causes heart damage.") that included the FDA as the source and engagement text (eg, "Within 3 months of quitting, your heart and lungs work better. Ready to be tobacco free? You can quit. For free nicotine replacement, call 1-800-QUIT-NOW"); (2) constituent-only messages that did not list the FDA as the source or include engagement text; and (3) a control condition with messages about littering cigarette butts. The primary outcome was the change in quit intentions (range, 1-4, with higher scores indicating stronger intentions) from pretest to day 16. Secondary outcome measures included daily smoking behaviors and quit attempts. A total of 789 participants (mean [SD] age, 43.4 [12.9] years; 483 [61.2%] women; 578 [73.3%] White; 717 [90.9%] non-Hispanic) were included in the study. The mean (SD) quit intention score was 2.5 (0.9) at pretest. Mean (SE) change in quit intention score from pretest to day 16 was 0.19 (0.07) points higher in the constituent plus engagement condition than in the control condition (P = .005) and 0.23 (0.07) points higher in the constituent-only condition compared with the control condition (P = .001). Participant reports of cigarettes smoked, forgone, and butted out were similar across study conditions at baseline and did not differ significantly at days 16 and 32 across study conditions. Viewing more messages was associated with an estimated decrease of 0.15 (SE, 0.01) cigarettes smoked per day per message viewed overall across conditions. To our knowledge, this is the first longitudinal test of cigarette constituent campaign messages in a national sample of adults who currently smoke. Messages about cigarette smoke constituents, with or without engagement text and source information, increased participants' intentions to quit, lending support to FDA efforts to educate consumers about such constituents. ClinicalTrials.gov Identifier: NCT03339206.

Abstract 14735: Volatile Organic Compounds Are Associated With Lower Ankle-Brachial Indexes in African Americans of the Jackson Heart Study

Introduction: Cigarette smoking is associated with peripheral artery disease (PAD) in African Americans (AA), but the association between cigarette constituents and PAD remain inadequately studied. We evaluated the effect of volatile organic compounds (VOC) acrolein and crotonaldehyde on ankle-brachial index (ABI) as well as related biomarkers in AA participants of the Jackson Heart Study. Methods: Urinary VOC concentrations were measured in a subset of participants at baseline including 345 self-reported current smokers and 718 never smokers. Multivariable linear regression assessed the association between ABI and VOC concentrations after adjustment for acute (cotinine) and chronic (pack-years) smoking measures in models 1 and 2, respectively. The degree of association was assessed after adjusting for possible mediation (Baron & Kenny procedure) by C-reactive protein (CRP), fibrinogen, and homocysteine (HCY) concentrations. VOC concentrations were natural log transformed for normal distribution and all models adjusted for relevant covariates. Results: The mean age of included participants was 52 years and 49% women. Individuals who smoked were more likely to be men, less educated, have prevalent cardiovascular disease, and lower mean ABI. In model 1, ABI was inversely associated with urinary acrolein and crotonaldehyde concentrations. Model 2 retained the inverse ABI association for both VOC. Crotonaldehyde was directly associated with CRP and HCY in models 1 and 2. In model 1, acrolein was associated with HCY (Table). Biomarker mediation of the VOC-ABI relationship was insignificant. Conclusions: Acrolein and crotonaldehyde concentrations are associated with lower ABI and higher measures of inflammation and thrombosis in a community-based sample of AA. These findings suggest reduction in VOC exposure may reduce the risk of PAD in AA who smoke cigarettes.

Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.

Electronic cigarette (e-cig) use is continuing to increase, particularly among youth never-smokers, and is used by some smokers to quit. The acute and chronic toxicity of e-cig use is unclear generally in the context of increasing reports of inflammatory-type pneumonia in some e-cig users. To assess lung effects of e-cigs without nicotine or flavors, we conducted a pilot study with serial bronchoscopies over 4 weeks in 30 never-smokers, randomized either to a 4-week intervention with the use of e-cigs containing only 50% propylene glycol (PG) and 50% vegetable glycerine or to a no-use control group. Compliance to the e-cig intervention was assessed by participants sending daily puff counts and by urinary PG. Inflammatory cell counts and cytokines were determined in bronchoalveolar lavage (BAL) fluids. Genome-wide expression, miRNA, and mRNA were determined from bronchial epithelial cells. There were no significant differences in changes of BAL inflammatory cell counts or cytokines between baseline and follow-up, comparing the control and e-cig groups. However, in the intervention but not the control group, change in urinary PG as a marker of e-cig use and inhalation was significantly correlated with change in cell counts (cell concentrations, macrophages, and lymphocytes) and cytokines (IL8, IL13, and TNFα), although the absolute magnitude of changes was small. There were no significant changes in mRNA or miRNA gene expression. Although limited by study size and duration, this is the first experimental demonstration of an impact of e-cig use on inflammation in the human lung among never-smokers.

Comparison of cigarette, little cigar, and waterpipe tobacco smoke condensate and e-cigarette aerosol condensate in a self-administration model

The pharmacological effects of tobacco products are primarily mediated by nicotine; however, research suggests that several non-nicotine tobacco constituents may alter the reinforcing effects of nicotine. This study evaluated the reinforcing effects of aqueous solutions of smoke/aerosol condensate from cigarettes, little cigars, electronic cigarettes (e-cigarettes), and waterpipe tobacco in a self-administration procedure to determine if abuse liability of these tobacco products differed. Adult male Sprague-Dawley rats (n = 64 total) were trained to self-administer intravenous nicotine (30 μg/kg/infusion) on a fixed ratio 5 schedule of reinforcement. Following nicotine dose-effect assessment (1, 7.5, 15, and 30 μg/kg/infusion), rats were given access to smoke/aerosol condensate derived from their assigned tobacco product. Rats responded for smoke/aerosol condensate containing 1, 7.5, 15, and 30 μg/kg/infusion nicotine, with the ratio of nicotine:non-nicotine constituents held constant across doses for each tobacco product. Responding for nicotine or smoke/aerosol condensate was also assessed on a progressive ratio schedule of reinforcement. Cigarette, little cigar, and e-cigarette smoke/aerosol condensates shifted the nicotine dose-effect curve leftward, whereas waterpipe tobacco smoke condensate shifted the dose-effect curve rightward. Smoke/aerosol condensate from all tobacco products produced similar levels of responding compared to nicotine alone during the progressive ratio phase. Results suggest that non-nicotine constituents in cigarettes, little cigars, and e-cigarettes differentially enhance nicotine’s reinforcing potency. In contrast, waterpipe tobacco blunted nicotine’s reinforcing potency, suggesting that it may contain unique constituents that dampen nicotine’s reinforcing effects.

Do Smokers Recall Source or Quitline on Cigarette Constituent Messages?

The Food and Drug Administration (FDA) is required under the Family Smoking Prevention and Tobacco Control Act to communicate the risks of tobacco use to the public. Little research exists about methods to communicate the constituents of tobacco in a media campaign. This research examines specific strategies to increase effectiveness of a media campaign for cigarette smoking adults about tobacco constituents by including engagement text about smoking cessation and FDA as the source of the campaign. In an eye tracking study of 211 current cigarette smokers, participants randomly viewed 4 cigarette constituent messages that varied engagement text for quitting (benefits of quitting and quitline number, presence, absence) and by FDA source (presence, absence). After the eye tracking session, participants were asked about recall of the national quitline number and the source of message. Participants in conditions with engagement text were significantly more likely than those in the no engagement conditions to recall the national quitline number. Few participants saw or recalled the FDA source. Engagement text for smoking cessation on constituent communication campaign messages significantly increases recall of the quitline, an important resource for smokers.

Propylene glycol, a major electronic cigarette constituent, attenuates the adverse effects of high-dose nicotine as measured by intracranial self-stimulation in rats

BackgroundNon-nicotine tobacco constituents may contribute to the abuse liability of tobacco products. We previously reported that electronic cigarette (EC) refill liquids containing nicotine and a range of non-nicotine constituents attenuated the anhedonic/aversive effects of nicotine in an intracranial self-stimulation (ICSS) model. The alcohol propylene glycol (PG) is a primary ingredient in these and other EC liquids, yet its abuse potential has not been established. The goal of this study was to evaluate the effects of parenteral administration of PG alone and PG combined with nicotine on ICSS in rats. Methods and resultsPG alone did not affect ICSS at concentrations up to 100%. PG (25% or 60%) did not affect nicotine’s reinforcement-enhancing (ICSS threshold-decreasing) effects at low to moderate nicotine doses, but attenuated nicotine’s reinforcement-attenuating/aversive (ICSS threshold-increasing) effects at a high nicotine dose. PG concentrations similar to those in EC liquid doses used in our previous studies (1% or 3%) modestly attenuated the ICSS threshold-elevating effects of a high nicotine dose. ConclusionsPG attenuated elevations in ICSS thresholds induced by high-dose nicotine, which may reflect an attenuation of nicotine’s acute aversive/anhedonic and/or toxic effects. PG may have contributed to the attenuated ICSS threshold-elevating effects of EC liquids reported previously. Further examination of PG in models of addiction and toxicity is needed to understand the consequences of EC use and to inform the development of EC product standards by the FDA.

Framework Convention on Tobacco Control Implementation in Nigeria: Lessons for Low- and Middle-Income Countries

Nigeria is a significant tobacco market and influential country in Africa. Nigeria ratified the WHO Framework Convention on Tobacco Control (FCTC) in 2005. We reviewed Nigeria's tobacco control legislation since 2000 and compliance of the National Tobacco Control Act (NTCA) 2015 with the FCTC. We reviewed the National Tobacco Control Bills 2011 (proposed by legislature) and 2014 (proposed by Executive), the NTCA 2015, and media stories on tobacco control from 2008 to 2017. The NTCA, despite being more comprehensive than Nigeria's first Tobacco Smoking (Control) law of 1990, maintained provisions promoted by the tobacco industry, for example: allowing designated smoking areas in hospitality venues, higher educational institutions, and transportation venues; a loophole in the advertising restrictions allowing communications with consenting adults; and having the Manufacturers Association of Nigeria (MAN) (which includes tobacco companies) on the National Tobacco Control Committee charged with working with the Ministry of Health to implement the law. The industry is also directly involved with the Standards Organisation of Nigeria (SON) in preparing regulations on cigarette constituents and emissions. In an unprecedented step globally, the law requires that implementing regulations be approved by the National Assembly, giving the industry another opportunity to weaken this law further by lobbying the legislators to favor the industry. As of January 2018, the law was still not being enforced. The NTCA can be strengthened through implementation guidelines still being developed. The industry should be prevented from interfering with through MAN and SON, as required by FCTC Article 5.3. The tobacco industry works to block Framework Convention on Tobacco Control implementation even after a country ratifies the treaty. The Nigerian case illustrates that it is essential for health authorities to remain vigilant and ensure that the tobacco industry does not play a decision-making role in the process of tobacco legislation and regulation either directly or indirectly. The unprecedented step of requiring approval of implementing regulations for the Nigerian law should not be allowed to become a precedent in other countries.

A systematic review of smoker and non-smoker perceptions of visually unappealing cigarette sticks.

INTRODUCTIONCigarette stick appearance can significantly contribute to perceptions of cigarette taste, harm, and appeal, and may be modified to reduce positive perceptions of cigarettes and other tobacco products. A systematic review was conducted to investigate how smokers and non-smokers identify cigarettes as being attractive or unattractive, and the resulting perceptions of cigarette appeal, perceived harm, and impact on quit intentions.METHODSEligible articles were identified using database searches conducted with a date range of January 1990 to May 2017 in PubMed, CINAHL, PsycINFO, Google Scholar and Web of Science. Articles were included if they evaluated participant (any smoking status) perceptions of visual cigarette stick attributes. We identified studies describing visual attributes of cigarette sticks and the resulting perceptions of participants. Changes or differences in quitting intentions, cigarette appeal, perceptions of taste, and cigarette harm, and the likelihood of smoking uptake were recorded. Data were grouped into two main categories: those of physical cigarette design, and those including health messages on cigarette sticks.RESULTSOf the 950 identified non-duplicated records, 9 matched the eligibility criteria. These studies were all conducted in developed countries, and largely enrolled adolescent and young adult smokers and non-smokers. Slim, lighter coloured and branded cigarettes were favoured over longer, broader, or darker coloured cigarettes, and those without any branding or embellishments. Health warnings including ‘Minutes of life lost’, ‘Smoking kills’, and the names of carcinogenic constituents in cigarettes, reduced cigarette attractiveness and increased participant quit intentions.CONCLUSIONSCigarette appeal and resulting smoking behaviours can be influenced by several visual attributes of individual cigarettes. Unappealing visual attributes of cigarette sticks, including modifications to the size and colour of cigarettes, and the inclusion of health warnings on cigarette sticks may serve as an effective tobacco control method, potentially leading to a reduction in tobacco use.

Cigarette constituent health communications for smokers: Impact of chemical, imagery, and source

Cigarette constituent health communications for smokers: Impact of chemical, imagery, and source

Effects of isolated tobacco alkaloids and tobacco products on deprivation-induced food intake and meal patterns in rats

The ability of smoking to reduce body weight serves as motivation for continued smoking. It is unclear to what extent non-nicotine constituents in cigarettes are contributing to the weight-reducing effect of smoking. The purpose of the current study was to examine the effects of nicotine and four minor tobacco alkaloids (nornicotine, cotinine, anatabine, and anabasine) on food intake, one of the key regulators of body weight. In addition, a smokeless tobacco extract (STE) and e-cigarette (EC) refill liquid were used to model the effects of actual tobacco product exposure on food intake. Male Holztman rats were trained to lever press for food pellets during daily 2h sessions in operant chambers. In Experiment 1, the effects of subcutaneous injections of saline, nicotine (0.25–1.00mg/kg), nornicotine (0.50–6.00mg/kg), cotinine (1.00–100.00mg/kg), anatabine (0.25–3.00mg/kg), and anabasine (0.50–4.00mg/kg) were assessed. In Experiment 2, rats from Experiment 1 were used to examine the effects of nicotine, STE, and EC liquid. All alkaloids, except cotinine, produced a dose-dependent reduction in overall food intake. The highest doses of all drugs significantly reduced latency and response rate to obtain the first pellet. At some doses, nicotine, anatabine, and nornicotine reduced food intake within the first 45min without compensatory increases in intake later in the session. STE and EC liquid produced dose dependent decreases in food intake similar to nicotine alone. These data suggest that minor tobacco alkaloids have appetite suppressant effects and warrant further investigation into their effects on body weight, energy intake, and energy expenditure under free-feeding conditions. However, findings with STE and EC liquid suggest that nicotine is the primary constituent in these products to affect food intake, whereas levels of minor alkaloids in these products may be too low to influence food intake.

Cigarette Constituent Health Communications for Smokers: Impact of Chemical, Imagery, and Source.

Communication campaigns are incorporating tobacco constituent messaging to reach smokers, yet there is a dearth of research on how such messages should be constructed or will be received by smokers. In a 2 × 2 × 2 experiment, we manipulated three cigarette constituent message components: (1) the toxic constituent of tobacco (arsenic vs. lead) with a corresponding health effect, (2) the presence or absence of an evocative image, and (3) the source of the message (FDA vs. no source). We recruited smokers (N = 1669, 55.4% women) via an online platform and randomized them to one of the eight message conditions. Participants viewed the message and rated its believability and perceived effectiveness, the credibility of the message source, and action expectancies (ie, likelihood of seeking additional information and help with quitting as a result of seeing the message). We found significant main effects of image, constituent, and source on outcomes. The use of arsenic as the constituent, the presence of an evocative image, and the FDA as the source increased the believability, source credibility, and perceived effectiveness of the tobacco constituent health message. Multiple elements of a constituent message, including type of constituent, imagery, and message source, impact their reception among smokers. Specifically, communication campaigns targeting smokers that utilize arsenic as the tobacco constituent, visual imagery, and the FDA logo may be particularly effective in changing key outcomes that are associated with subsequent attitude and behavioral changes. This article describes how components of communication campaigns about cigarette constituents are perceived. Multiple elements of a tobacco constituent message, including type of constituent, image, and message source may influence the reception of messages among current smokers. Communication campaigns targeting smokers that utilize arsenic as the tobacco constituent, visual imagery, and the FDA logo may be particularly effective in changing key outcomes among smokers. The effects of such campaigns should be examined, as well as the mechanisms through which such campaigns affect change.

Increases in Cigarette Consumption and Decreases in Smoking Intensity When Nondaily Smokers Are Provided With Free Cigarettes.

Studies testing novel tobacco products often provide participants with free product and assess consumption. Some, but not all, studies find that providing free cigarettes increases smoking. We tested changes in smoking when free cigarettes were provided to nondaily, intermittent smokers, who constitute one-third of US adult smokers. Cigarette consumption was assessed by Time-Line Follow-Back in 235 intermittent smokers for two 2-week periods: when providing their own cigarettes and when provided own-brand cigarettes for free. Smoking topography and carbon monoxide boost were assessed for one cigarette at the end of each period. Cigarette consumption increased significantly, by 66% (from 1.98 to 3.28 cigarettes per day), when cigarettes were available for free; both the number of days the subjects smoked and the number of cigarettes on those days increased. The increases were significantly greater among African Americans, those Fagerström Tobacco Nicotine Dependence scores >0, those with incomes less than US $25,000 per year, those who engaged in greater conscious restraint of smoking, and for smokers of menthol cigarettes, or "longs." Smoking intensity (smoke volume, by topography) and carbon monoxide boost decreased significantly when cigarettes were provided for free. Providing intermittent smokers with free cigarettes substantially increased their smoking while decreasing smoking intensity. The increases in smoking varied according to multiple individual and cigarette-type differences. These phenomena may complicate interpretation of studies that compare consumption of a free test product with cigarette consumption or constituent exposure when smokers are providing their own cigarettes. They also suggest that cigarette cost and variations in low-level dependence and in smoking restraint are factors in nondaily smoking. The study shows that providing nondaily smokers with free cigarettes increases cigarette consumption, but does differentially for different subgroups and cigarette types, while also decreasing smoking intensity. This suggests the value of using free-cigarette baseline data in studies where interventions provide free cigarettes.

Effective Message Elements for Disclosures About Chemicals in Cigarette Smoke.

Cigarette smoke contains at least 93 chemicals or "constituents" that the Food and Drug Administration has identified as harmful and potentially harmful constituents to human health. Our study sought to identify which constituent disclosure message elements are most effective in discouraging people from smoking. Three hundred eighty eight current smokers aged 18 and older completed an online survey in February 2015. We randomized participants to respond to one of two sets of 13 toxic products that contain cigarette constituents and 25 health effects associated with cigarette constituents. Products that elicited the most discouragement were those with lower chances of exposure (e.g., explosives), followed by products with possible exposure (e.g., rat poison), and products with a high likelihood of exposure (e.g., floor cleaner). Awareness of toxic products that constituents are found in (p < .001) and low exposure products (p < .001) were associated with higher discouragement. Health effects that people had heard are caused by cigarette smoke constituents elicited higher discouragement from smoking cigarettes (p < .001). Cancer was associated with higher discouragement relative to respiratory, cardiovascular, and reproductive health effects (all p < .001). Cigarette smoke constituent messages may be more effective at discouraging smoking if they include information about carcinogenic health effects (e.g., mouth cancer and lung tumors) and low exposure toxic products (e.g., explosives and radioactive material) as message elements. Our study identified health effects and toxic products, especially cancers and rarely encountered toxic products, that may discourage smoking when included in disclosure messages. By constructing messages that communicate the harms associated with tobacco use by contextualizing those harms in terms of specific constituents, tobacco education messaging efforts may be increasingly successful.

"My First Thought was Croutons": Perceptions of Cigarettes and Cigarette Smoke Constituents Among Adult Smokers and Nonsmokers.

Understanding what people think about harmful and potentially harmful constituents in cigarettes and cigarette smoke has new urgency given legislation requiring US Food and Drug Administration (FDA) to disclose constituent information. Our study sought to obtain qualitative information on what people think about these constituents and the language they use to talk about them. We conducted six focus groups in 2014 with 40 adults in North Carolina. Open-ended questions focused on cigarette and cigarette smoke constituents in general and on the 18 constituents on the FDA's abbreviated list. We coded the transcripts for emergent themes, and all four coders discussed themes until we reached consensus. Participants knew that cigarette smoke contains chemicals but did not know how many chemicals nor what those chemicals are, beyond tar and nicotine. Dangers of constituents mentioned included "chemicals," physical disease, and addiction. Participants incorrectly believed harmful constituents came primarily from tobacco companies' additives. For unfamiliar constituents, people tried to make associations based on similar-sounding words. Recognizable constituents that participants associated with health harms most discouraged them from wanting to smoke. Most participants wanted to know health harms associated with constituents and what else the chemicals were in. Participants showed enthusiasm for learning more information about constituents, and also showed substantial misunderstandings about the source of harmful constituents. Our findings contribute to the limited body of research on adults' knowledge and perceptions of cigarette smoke constituents and can aid the FDA as it plans to disclose constituent information to the public. Our study provides information about adults' understanding of cigarette smoke constituents and what adults would like to know about these constituents. This information can help communication campaigns describe cigarette smoke constituents in a way that discourages people from wanting to smoke.

Cigarette smoke condensate and individual constituents modulate DNA methyltransferase expression in human liver cells.

Objectives:Previous studies found higher expression levels of DNA methyltransferase 1 in liver samples from smokers compared to those from non-smokers. In contrast, expression levels of DNA methyltransferase 3a and DNA methyltransferase 3b were similar in smokers and non-smokers. This study extends these studies to establish a causal linkage to cigarette smoke exposure by examining whether DNA methyltransferase expression is modulated by cigarette smoke condensate.Methods:These experiments were conducted in an in vitro system using HepG2 human liver cells. The dose range of cigarette smoke condensate was 0.1–120 µg/mL. The duration of exposure was up to 72 h.Results:In a 24-h exposure, DNA methyltransferase 1 expression was found to increase significantly in a dose-dependent manner (greater than threefold at 100 µg/mL cigarette smoke condensate). Expression levels of DNA methyltransferase 3a and DNA methyltransferase 3b were, however, not affected under these conditions. The effect of two cigarette constituents, nicotine and cotinine, on DNA methyltransferase 1 expression was also examined. Nicotine exposure significantly increased DNA methyltransferase 1 expression in a dose-dependent manner (greater than twofold at 50 µM). However, under these conditions, cotinine did not increase DNA methyltransferase 1 expression.Conclusion:These results clearly provide additional support of the modulating effect of cigarette smoke on DNA methyltransferase 1 expression. Given the potential of alterations in DNA methyltransferase expression to affect cellular function, this pathway may play a critical role in cigarette smoke-induced toxicity.

Abstract 3127: Cigarette smoke condensate (CSC) induces differential expression and promoter methylation profiles of critical genes involved in lung cancer in NL-20 lung cells in vitro: Short-term and chronic exposure

Abstract Lung cancer is the leading cause of cancer deaths in the United States. Smoking accounts for a large number of those deaths. Recently, the Food and Drug Administration has been given authority to regulate any new cigarette products coming to market and further demonstrate the harm caused by constituents in cigarettes or those chemicals created from smoking. Establishing early diagnostic markers are critical to effective prevention programs. This study examined the effects of cigarette smoke condensate on expression and promoter methylation profile of critical genes involved in various stages of lung cancer development, such as E-cadherin (ECAD), O6-mehyl-guanine-DNA methyltransferase (MGMT), and RASSF1A. NL-20 cells were treated with 0.1, 1, 10 or 100 µg/ml of CSC for 24, 48 and 72 hrs for short-term exposures. ECAD showed a significant decrease in expression after 72 hrs with both 10 and 100 µg/ml CSC. This decrease in expression correlated to hypermethylation of the ECAD promoter at both concentrations using MSP analysis. MGMT expression increased only with the concentration of 100 µg/ml CSC at all time points. This correlated to an unmethylated profile of the promoter at this concentration. RASSF1A promoter profile was methylated in the control samples. However, when treated with 10 or 100 µg/ml CSC, an unmethylated promoter profile was noted. This correlated to increased expression of RASSF1A at both the 10 and 100 µg/ml concentrations. No changes were noted at 0.1 or 1 µg/ml of CSC in NL-20 lung cells. For chronic studies, the cells were exposed for 30 days with 10 or 100 µg/ml CSC, with media changes every three days adding new CSC. After 30 days, cells showed morphological changes associated with transformation. Foci were noted. These cells were further analyzed for further changes in critical genes involved in lung cancer. This study provides critical data showing epigenetic regulation of critical genes involved in DNA repair, invasion and tumor suppressor with treatment of lung cells with CSC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3127. doi:1538-7445.AM2012-3127