Cigarette Tar Research Articles

Health risks of environmentally persistent free radicals in atmospheric particulate matter during the spring festival travel season in Tainan, Taiwan.

Environmentally persistent free radicals (EPFRs) and polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants in atmospheric particulate matter that are detrimental to human health. This study collected atmospheric particulate matter during and after the spring festival travel season in Tainan, Taiwan, from various locations and analyzed the carbon composition and PAH isomeric ratios to identify the sources. In this study, EPFR concentrations were measured using electron paramagnetic resonance spectroscopy, with the highest concentration found to be 3.04 × 10(12) spins/m3. EPFRs contained predominantly oxygen-centered radicals in PM2.5, which are mainly existed in PM1. The results show that EPFR concentrations on PM, measured per unit volume (spins/m3) or mass (spins/g), were highest during the spring festival travel season. The daily inhalation exposure to the sum of EPFRs and PAHs in PM2.5 was estimated to be equivalent to inhaling 0.11-0.15 cigarette tar EPFRs per day. This report is the first to document EPFRs in environmental atmospheric particulate matters in Taiwan, which has significantly contributed to local air pollution control and reduced exposure risks to public health in Tainan.

Composition, structural, and thermal analysis of cellulose, hemicellulose, and lignin of reconstituted cut stems in tobacco

In order to encourage effective recycling of tobacco resources in the industry and successfully enhance the quality of reconstituted cut stems (GS30). This study investigates the thermal, structural, and material composition of GS30. It was found that compared with high-quality tobacco leaves and cut stems, the contents of important macromolecules including cellulose, hemicellulose and lignin in GS30 were 21.74 ± 1.14 %, 3.66 ± 0.56 %, and 1.69 ± 0.46 % respectively. Its content is smaller than that of blank cut stems but similar to high-quality tobacco leaves. The important macromolecular structures were further analyzed for their surface morphology and crystal structure using FTIR, XRD, SAXS, and SEM. After analyzing the thermal cracking behavior of GS30 through PY-GC-MS, it was found that GS30 has four weight loss stages and thermal cracking releases near 30 types of aroma substances, showing obvious advantages in releasing aromatic gases. This demonstrates that the structure of GS30 obtained from secondary processing of discarded tobacco leaves is loose and easy to burn and decompose, which can effectively reduce the release of cigarette tar.

Dimethyl Sulfoxide: An Ideal Electrochemical Probe for Hydroxyl Radical Detection.

In situ and real-time determination of hydroxyl radicals (•OH) in physiological and pathological processes is a great challenge due to their ultrashort lifetime. Herein, an electrochemical method was developed by using dimethyl sulfoxide (DMSO) as a trapping probe for rapid determination of •OH in aqueous solution. When DMSO reacted with •OH, an intermediate product methane sulfinic acid (MSIA) was formed, which can be electrochemically oxidized to methanesulfonic acid (MSA) on the glassy carbon electrode (GCE), resulting in a distinct voltammetric signal that is directly proportional to the concentration of •OH. Other commonly encountered reactive oxygen species (ROS), including hypochlorite anions (ClO-), superoxide anions (O2•-), sulfate radicals (SO4•-), and singlet oxygen (1O2), have showed no interference for •OH determination. Thus, an electrochemical method was developed for the determination of •OH, which exhibits a wide linear range (0.4-5120 μM) and a low limit detection of 0.13 μM (S/N = 3) and was successfully applied for the quantification of •OH in aqueous extracts of cigarette tar (ACT). Alternatively, the same reaction mechanism is also applicable for the determination of DMSO, in which a linear range of 40-320 μM and a detection limit 13.3 μM (S/N = 3) was achieved. The method was used for the evaluation of DMSO content in cell cryopreservation medium. This work demonstrated that DMSO can serve as an electrochemical probe and has valuable application potential in radical study, biological research, and environmental monitoring.

Cigarette tar accelerates atherosclerosis progression via RIPK3-dependent necroptosis mediated by endoplasmic reticulum stress in vascular smooth muscle cells

BackgroundTar is the main toxic of cigarettes, and its effect on atherosclerosis progression and the underlying mechanisms remain largely unknown. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and plaque vulnerability. The present study sought to investigate the mechanism of atherosclerosis progression through tar-induced VSMC necroptosis, a recently described form of necrosis.MethodsThe effect of tar on atherosclerosis progression and VSMC necroptosis was examined in ApoE−/− mice and cultured VSMCs. The role of necroptosis in tar-induced plaque development was evaluated in RIPK3-deletion mice (ApoE−/−RIPK3−/−). The key proteins of necroptosis in carotid plaques of smokers and non-smokers were also examined. Quantitative proteomics of mice aortas was conducted to further investigate the underlying mechanism. Pharmacological approaches were then applied to modulate the expression of targets to verify the regulatory process of tar-induced necroptosis.ResultsTar administration led to increased atherosclerotic plaque area and reduced collagen and VSMCs in ApoE−/− mice. The expression of RIPK1、RIPK3、and MLKL in VSMCs of plaques were all increased in tar-exposed mice and smokers. RIPK3 deletion protected against VSMC loss and plaque progression stimulated by tar. In mechanistic studies, quantitative proteomics analysis of ApoE−/− mice aortas suggested that tar triggered endoplasmic reticulum (ER) stress. PERK-eIF2α-CHOP axis was activated in tar-treated VSMCs and atherosclerotic plaque. Inhibition of ER stress using 4PBA significantly reduced plaque progression and VSMC necroptosis. Further study revealed that ER stress resulted in calcium (Ca2+) release into mitochondria and cytoplasm. Elevated Ca2+ levels lead to mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, which consequently promote RIPK3-dependent necroptosis. In addition, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated by cytosolic Ca2+ overload binds to RIPK3, accounting for necroptosis.ConclusionThe findings revealed that cigarette tar promoted atherosclerosis progression by inducing RIPK3-dependent VSMC necroptosis and identified novel avenues of ER stress and Ca2+ overload.

Cigarette tar mediates macrophage ferroptosis in atherosclerosis through the hepcidin/FPN/SLC7A11 signaling pathway.

Despite the known promotional effects of cigarette smoking on progression of atherosclerosis (AS), tar as the most dominant toxic component in cigarette smoking has been little studied. Understanding the potential role and mechanisms of tar in AS may be a prerequisite for future reductions in cardiovascular morbidity and mortality. Male ApoE-/- mice were fed with high-fat diet and injected intraperitoneally with cigarette tar (40mg/kg/day) for 16 weeks. The results showed that cigarette tar significantly promoted the formation of lipid-rich plaques with larger necrotic cores and less fibrous, and caused severe iron overload and lipid peroxidation in AS lesions. Moreover, tar significantly upregulated the expression of hepcidin and downregulated FPN and SLC7A11 of macrophages in AS plaques. Ferroptosis inhibitor (FER-1 and DFO) treatment, hepcidin-knockdown or SLC7A11-overexpression reversed above changes, thereby delaying the progression of atherosclerosis. In vitro, the use of FER-1, DFO, si-hepcidin, and ov-SLC7A11 increased cell viability and inhibited iron accumulation, lipid peroxidation and GSH depletion in tar treated macrophages. These interventions also inhibited the tar induced upregulation of hepcidin, and increased the expression of FPN, SLC7A11, and GPX4. Furthermore, NF-κB inhibitor reversed the regulatory effect of tar on hepcidin/FPN/SLC7A11 axis, and then inhibiting macrophage ferroptosis. These findings indicated that cigarette tar promotes atherosclerosis progression by inducing macrophage ferroptosis via NF-κB-activated hepcidin/FPN/SLC7A11 pathway.

A Novel Chemiluminescent Method for Efficient Evaluation of Heterogeneous Fenton Catalysts Using Cigarette Tar

The evaluation of the catalytic capacity of catalysts is indispensable research, as catalytic capacity is a crucial factor to dictate the efficiency of heterogeneous Fenton catalysis. Herein, we obtained cigarette tar-methanol extracts (CTME) by applying methanol to cigarette tar and found that CTME could cause CL reactions with Fe2+/H2O2 systems in acidic, neutral, and alkaline media. The CL spectrum experiment indicated that the emission wavelengths of the CTME CL reaction with Fe2+/H2O2 systems were about 490 nm, 535 nm, and 590 nm. Quenching experiments confirmed that hydroxyl radicals (•OH) were responsible for the CL reaction for CTME. Then the CL property of CTME was applied in-situ to rapidly determine the amounts of •OH in tetrachloro-1,4-benzoquinone (TCBQ)/H2O2 system in acidic, neutral and alkaline media, and the CL intensities correlated the best (R2 = 0.99) with TCBQ concentrations. To demonstrate the utility of the CTME CL method, the catalytic capacity of different types and concentrations of catalysts in heterogeneous Fenton catalysis were examined. It was found that the order of CL intensities was consistent with the order of degradation efficiencies of Rhodamine B, indicating that this method could distinguish the catalytic capacity of catalysts. The CTME CL method could provide a convenient tool for the efficient evaluation of the catalytic capacity of catalysts in heterogeneous Fenton catalysis.

Characteristics of Environmentally Persistent Free Radicals in PM2.5 and the Influence of Air Pollutants in Shihezi, Northwestern China.

Environmentally persistent free radicals (EPFRs) are a kind of hazardous substance that exist stably in the atmosphere for a long time. EPFRs combined with fine particulate matter (PM2.5) can enter the human respiratory tract through respiration, causing oxidative stress and DNA damage, and they are also closely related to lung cancer. In this study, the inhalation risk for EPFRs in PM2.5 and factors influencing this risk were assessed using the equivalent number of cigarette tar EPFRs. The daily inhalation exposure for EPFRs in PM2.5 was estimated to be equivalent to 0.66–8.40 cigarette tar EPFRs per day. The concentration level and species characteristics were investigated using electron paramagnetic resonance spectroscopy. The concentration of EPFRs in the study ranged from 1.353–4.653 × 1013 spins/g, and the types of EPFRs were mainly oxygen- or carbon-centered semiquinone-type radicals. Our study showed that there is a strong correlation between the concentrations of EPFRs and conventional pollutants, except for sulfur dioxide. The major factors influencing EPFR concentration in the atmosphere were temperature and wind speed; the higher the temperature and wind speed, the lower the concentration of EPFRs. The findings of this study provide an important basis for further research on the formation mechanism and health effects of EPFRs.

Evaluation of Sertraline as an antioxidant, anti-inflammatory and anticataract

Sertraline can also protect against environmental causes of free radicals such as smoking. Cigarette tar is a source of free radicals which has been found to damage erythrocyte membranes. It was also found that Sertraline and its conjugate metabolites could protect erythrocytes from the membranous damage that is caused by smoking. The ability of Sertraline is claimed to exert many beneficial effects on health, including protection against various diseases such as osteoporosis, lung cancer, and cardiovascular disease. The studies showed that there has been a reduction in the risk of cardiovascular disease in subjects, who had a high intake of flavonoids. Progressive disorder of the lung parenchyma and airways or also known as chronic obstructive pulmonary disease (COPD) which happens to be the third-leading cause of death in the USA. Therapies thus far for COPD, unfortunately, is said to be partially effective with possibilities of side effects.

956Cumulative low-tar exposure was still associated with increased lung cancer risk from Japanese case-control study

Abstract Background Tar concentration in cigarette brands is chronologically decreasing in the USA and Japan. However, studies investigating lung cancer risk with cumulative tar exposure in Western and Asian countries are insufficient. To investigate the risk of lung cancer with cumulative cigarette tar exposure, we conducted a case-control study among Japanese current smokers. Methods This study used data from the US-Japan lung cancer joint study in 1993–1998. The number of the subjects was 282 histologically confirmed lung cancer cases and 162 hospital and 227 community controls, and two control groups were combined. The information regarding tar concentration was obtained from the published documents and additional estimation using the equation of regression. Cumulative tar concentration was calculated by multiplying the annual value of tar concentration by year and brand. The odds ratios (ORs) and 95% confidence intervals for lung cancer with cumulative tar exposure were estimated using a logistic model. Results The OR with cumulative tar exposure was higher in higher exposed smokers (>45.6 × 105mg, 8.10, 4.74–13.7) than in lower exposed smokers (≤45.6 × 105mg, 3.37, 1.92–5.92), and increasing trend of the ORs was significant (p < 0.001). The stratification analysis showed higher ORs among those with higher cumulative tar exposure regardless of inhalation, duration of smoking filtered cigarettes, and histological type. Conclusions This study showed that cumulative tar exposure is a dose-dependent indicator for lung cancer risk, and low-tar exposure was still associated with increased cancer risk. Key messages Low-tar tobacco is still associated with increased lung cancer risk.

Hydroquinone Exposure Worsens Rheumatoid Arthritis through the Activation of the Aryl Hydrocarbon Receptor and Interleukin-17 Pathways.

Rheumatoid arthritis (RA) development is strongly associated with cigarette smoke exposure, which activates the aryl hydrocarbon receptor (AhR) as a trigger for Th17 inflammatory pathways. We previously demonstrated that the exposure to hydroquinone (HQ), one of the major compounds of cigarette tar, aggravates the arthritis symptomatology in rats. However, the mechanisms related to the HQ-related RA still remain elusive. Cell viability, cytokine secretion, and gene expression were measured in RA human fibroblast-like synoviocytes (RAHFLS) treated with HQ and stimulated or not with TNF-α. Antigen-induced arthritis (AIA) was also elicited in wild type (WT), AhR −/− or IL-17R −/− C57BL/6 mice upon daily exposure to nebulized HQ (25ppm) between days 15 to 21. At day 21, mice were challenged with mBSA and inflammatory parameters were assessed. The in vitro HQ treatment up-regulated TNFR1, TNFR2 expression, and increased ROS production. The co-treatment of HQ and TNF-α enhanced the IL-6 and IL-8 secretion. However, the pre-incubation of RAHFLS with an AhR antagonist inhibited the HQ-mediated cell proliferation and gene expression profile. About the in vivo approach, the HQ exposure worsened the AIA symptoms (edema, pain, cytokines secretion and NETs formation) in WT mice. These AIA effects were abolished in HQ-exposed AhR −/− and IL-17R −/− animals though. Our data demonstrated the harmful HQ influence over the onset of arthritis through the activation and proliferation of synoviocytes. The HQ-related RA severity was also associated with the activation of AhR and IL-17 pathways, highlighting how cigarette smoke compounds can contribute to the RA progression.

Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells.

Age-related macular degeneration (AMD) is a retinal disease leading to impaired vision. Cigarette smoke increases the risk for developing AMD by causing increased reactive oxygen species (ROS) production and damage in the retinal pigment epithelium (RPE). We have previously shown that the cigarette tar component hydroquinone causes oxidative stress in human RPE cells. In the present study, we investigated the propensity of hydroquinone to induce the secretion of interleukin (IL)-1β and IL-18. The activation of these cytokines is usually regulated by the Nucleotide-binding domain, Leucine-rich repeat, and Pyrin domain 3 (NLRP3) inflammasome. ARPE-19 cells were exposed to hydroquinone, and cell viability was monitored using the lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt (MTT) assays. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of proinflammatory cytokines IL-1β and IL-18 as well as NLRP3, caspase-1, and poly (ADP-ribose) polymerase (PARP). Hydroquinone did not change IL-1β release but significantly increased the secretion of IL-18. Cytoplasmic NLRP3 levels increased after the hydroquinone treatment of IL-1α-primed RPE cells, but IL-18 was equally released from primed and nonprimed cells. Hydroquinone reduced the intracellular levels of PARP, which were restored by treatment with the ROS scavenger N-acetyl-cysteine (NAC). NAC concurrently reduced the NLRP3 levels but had no effect on IL-18 release. In contrast, the NADPH oxidase inhibitor ammonium pyrrolidinedithiocarbamate (APDC) reduced the release of IL-18 but had no effect on the NLRP3 levels. Collectively, hydroquinone caused DNA damage seen as reduced intracellular PARP levels and induced NLRP3-independent IL-18 secretion in human RPE cells.

Association of Cigarette Type and Nicotine Dependence in Patients Presenting for Lung Cancer Screening

Over decades, there have been several alterations to cigarettes, including the addition of filters and flavoring. However, lung cancer remains the leading cause of cancer-related death in the United States. The aim of this study was to examine the association of type of cigarette on nicotine dependence in the setting of lung cancer screening. This study is a secondary analysis of the American College of Radiology Imaging Network arm of the National Lung Screening Trial. Tobacco dependence was evaluated by using the Fagerstrӧm Test for Nicotine Dependence, the Heaviness of Smoking Index, and time to first cigarette. Clinical outcomes, including nicotine dependence and tobacco abstinence, were assessed with descriptive statistics and χ2 tests, stratified according to cigarette tar level, flavor, and filter. Logistic regression was used to study the influence of variables on smoking abstinence. More than one-third of individuals presenting for lung cancer screening are highly addicted to nicotine and smoke within 5min of waking up. Smokers of unfiltered cigarettes were more nicotine dependent compared with filtered cigarette smokers (OR, 1.32; P< .01). Although smokers of light/ultralight cigarettes had lower dependence (OR, 0.76, P< .0001), there was no difference in smoking abstinence compared with regular cigarette smokers. There was no difference in outcomes when comparing smokers of menthol vsunflavored cigarettes. In a screening population, the type of cigarette smoked is associated with different levels of dependence. Eliciting type of cigarette and time to first cigarette has the potential to allow for tailored tobacco treatment interventions within this context.

Cumulative cigarette tar exposure and lung cancer risk among Japanese smokers.

Tar concentration in cigarette brands is chronologically decreasing in the USA and Japan. However, studies investigating lung cancer risk with cumulative tar exposure in Western and Asian countries are insufficient. To investigate the risk of lung cancer with cumulative cigarette tar exposure, we conducted a case-control study among Japanese current smokers. This study used data from the US-Japan lung cancer joint study in 1993-1998. A total of 282 subjects with histologically confirmed lung cancer and 162 hospital and 227 community controls were included in the study, and two control groups were combined. The information regarding tar concentration was obtained from the published documents and additional estimation using the equation of regression. Cumulative tar concentration was calculated by multiplying the annual value of brand-specific tar concentration by years of smoking. The odds ratios and 95% confidence intervals for lung cancer with cumulative tar exposure were estimated using a logistic model. The odds ratios for lung cancer with both lower (1-59.8×105mg) and higher (>59.8×105mg) total cumulative tar exposure were statistically significant (3.81, 2.23-6.50 and 11.64, 6.56-20.67, respectively) with increasing trend (P<0.001). The stratification analysis showed higher odds ratios in subjects with higher cumulative tar exposure regardless of inhalation, duration of smoking filtered cigarettes and histological type. This study showed that cumulative tar exposure is a dose-dependent indicator for lung cancer risk, and low-tar exposure was still associated with increased cancer risk.

Risk evaluation of environmentally persistent free radicals in airborne particulate matter and influence of atmospheric factors.

Environmentally persistent free radicals (EPFRs) was considered unrecognized composition of air pollutants and might help explain the long-standing medical mystery of why non-smokers develop tobacco-related diseases like lung cancer. EPFRs in airborne fine particulate matter (PM2.5) can induce oxidative and DNA damage when inhaled. We assessed the inhalation risk of EPFRs in PM2.5 and factors influencing this risk in Beijing as a large city with frequent haze events. The average concentration of EPFRs in PM2.5 was 6.00×1017 spins/m3 in spring, autumn, and winter; lower concentrations were recorded in the summer. To estimate the daily inhalation risk of EPFRs in PM2.5, we used the equivalent EPFRs in cigarette tar. The average daily inhalation exposure of EPFRs in PM2.5 was estimated to be the equivalent of 33.1 cigarette tar EPFRs per day (range: 0.53-226.9) during both haze and non-haze days. The major factors influencing EPFR concentrations in the atmosphere were precipitation and humidity, which reduced airborne concentrations. Levels of PM2.5 and carbon monoxide were positively correlated with EPFR concentrations. The health risks of inhaling airborne EPFRs could be significant and should be recognized and quantified.

Association of Cigarette Type With Lung Cancer Incidence and Mortality

This study uses data from the National Lung Screening Trial to investigate the association of cigarette tar level, flavor, and filter status with lung cancer diagnosis, mortality, and all-cause mortality.

β-Carotene Supplementation and Lung Cancer Incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: The Role of Tar and Nicotine.

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated that β-carotene supplementation increases lung cancer incidence in smokers. Further, cigarettes with higher tar and nicotine content are associated with a higher risk of lung cancer. However, no studies have examined whether the increased risk associated with β-carotene supplementation in smokers varies by the tar or nicotine content of cigarettes. The ATBC Study was a randomized, double-blind intervention trial conducted in southwest Finland. A total of 29 133 male smokers, aged 50-69 years, were enrolled and randomly assigned to one of four groups (α-tocopherol, β-carotene, both, or placebo). Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of lung cancer risk by β-carotene trial assignment stratified by a priori categories of cigarette tar and nicotine content. The β-carotene supplementation group had significantly higher risk of developing lung cancer in all categories of tar content (yes vs. no β-carotene supplementation-ultralight cigarettes [≤7 mg tar]: HR = 1.31, 95% CI = 0.91 to 1.89; nonfiltered cigarettes [≥21 mg tar]: HR = 1.22, 95% CI = 0.91 to 1.64; p for interaction = .91). Similarly, there was no interaction with nicotine content (yes vs. no β-carotene supplementation-ventilated cigarettes [≤0.8 µg nicotine]: HR = 1.23, 95% CI = 0.98 to 1.54; nonfiltered cigarettes [≥1.3 µg nicotine]: HR = 1.22, 95% CI = 0.91 to 1.64; p for interaction = .83). These findings support the conclusion that supplementation with β-carotene increases the risk of lung cancer in smokers regardless of the tar or nicotine content of cigarettes smoked. Our data suggest that all smokers should continue to avoid β-carotene supplementation. Previous studies demonstrated that β-carotene supplementation increases risk of lung cancer in smokers. This study moves the field forward by examining the potential for modification of risk of lung cancer with different levels of tar and nicotine in cigarettes smoked, as interaction with carcinogens in these components of cigarette smoke is hypothesized to be the mechanism by which β-carotene increases risk. Our study provides evidence that the increased risk of lung cancer in smokers who take β-carotene supplements is not dependent upon the tar or nicotine level of cigarettes smoked and suggests that all smokers should continue to avoid β-carotene supplementation.

Abstract 2289: B-carotene supplementation and lung cancer risk in the ATBC Study: the role of tar and nicotine

Abstract Background: Globally, lung cancer is the most common cancer and the leading cause of cancer death. Early observational studies reported a protective association between intake of β-carotene rich vegetables and lung cancer risk, which led to interest in β-carotene supplementation as a potential chemopreventive strategy, particularly in high-risk populations such as cigarette smokers. A large randomized controlled trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, demonstrated that β-carotene supplementation increased lung cancer incidence by 18% in smokers, and led to an 8% excess in overall mortality. It is also well-documented that cigarettes with higher (versus lower) tar and nicotine content are associated with a higher risk of lung cancer. To our knowledge, however, no studies have examined whether the increased risk associated with β-carotene supplementation in smokers varies by cigarette tar or nicotine content. Methods: The ATBC Study was a randomized, double-blind vitamin supplementation trial conducted among 29,133 male smokers in southwest Finland. Participants were randomly assigned to one of four groups in a 2x2 factorial design (α-tocopherol alone, β-carotene alone, both supplements, or placebo). A detailed smoking history was collected at baseline, including brands of cigarettes smoked (for which machine measured tar and nicotine content was available). Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of lung cancer risk by trial B-carotene assignment stratified by a priori categories of cigarette tar (ultra-light ≤7 mg, light 8-14 mg, medium/regular 15-20 mg, high/non-filtered/self-made &amp;gt;20 mg) and nicotine content (ventilated filtered ≤0.8 µg, unventilated filtered 0.8-1.3 µg, non-filtered &amp;gt;1.3 µg). Statistical interaction was estimated using the likelihood ratio test. Results: The β-carotene supplemented arm had a statistically significantly higher risk of developing lung cancer in all categories of tar content [yes vs. no β-carotene supplementation - ultra-light: HR=1.31 95% CI=0.91-1.89; non-filtered: HR=1.22 95% CI=0.91-1.64; p-interaction=0.91]. Similarly, there was no apparent interaction with cigarette nicotine content [yes vs. no β-carotene supplementation - ventilated cigarettes: HR=1.23, 95% CI=0.98-1.54; non-filtered cigarettes: HR=1.22, 95% CI=0.91-1.64; p-interaction=0.83]. Conclusion: These findings indicate that supplementation with β-carotene increases lung cancer incidence in smokers regardless of the tar or nicotine content of cigarettes smoked. Our data suggest that all smokers, regardless of the type of cigarette smoked, should continue to avoid β-carotene supplementation. Citation Format: Pooja Middha, Stephanie J. Weinstein, Satu Männistö, Demetrius Albanes, Alison M. Mondul. B-carotene supplementation and lung cancer risk in the ATBC Study: the role of tar and nicotine [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 2289. doi:10.1158/1538-7445.AM2017-2289

Case-control study of cumulative cigarette tar exposure and lung and upper aerodigestive tract cancers.

The development of comprehensive measures for tobacco exposure is crucial to specify effects on disease and inform public health policy. In this population-based case-control study, we evaluated the associations between cumulative lifetime cigarette tar exposure and cancers of the lung and upper aerodigestive tract (UADT). The study included 611 incident cases of lung cancer; 601 cases of UADT cancers (oropharyngeal, laryngeal and esophageal cancers); and 1,040 cancer-free controls. We estimated lifetime exposure to cigarette tar based on tar concentrations abstracted from government cigarette records and self-reported smoking histories derived from a standardized questionnaire. We analyzed the associations for cumulative tar exposure with lung and UADT cancer, overall and according to histological subtype. Cumulative tar exposure was highly correlated with pack-years among ever smoking controls (Pearson coefficient = 0.90). The adjusted odds ratio (95% confidence limits) for the estimated effect of about 1 kg increase in tar exposure (approximately the interquartile range in all controls) was 1.61 (1.50, 1.73) for lung cancer and 1.21 (1.13, 1.29) for UADT cancers. In general, tar exposure was more highly associated with small, squamous and large cell lung cancer than adenocarcinoma. With additional adjustment for pack-years, positive associations between tar and lung cancer were evident, particularly for small cell and large cell subtypes. Therefore, incorporating the composition of tobacco carcinogens in lifetime smoking exposure may improve lung cancer risk estimation. This study does not support the claim of a null or inverse association between "low exposure" to tobacco smoke and risk of these cancer types.

Analysis of polycyclic aromatic hydrocarbons in cigarette samples using gel permeation chromatography clean-up by gas chromatography–tandem mass spectrometry

A new method using gel permeation chromatography (GPC) as clean-up by gas chromatography coupled to a triple quadrupole tandem mass spectrometry (GC–MS/MS) was established to measure the concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) in cigarette samples. GPC clean-up was employed to purify cigarette mainstream smoke samples collected from cigarettes in China, giving cleaner final extracts than traditional solid phase extraction (SPE). GC–MS/MS with a “pseudo” multiple reactive monitoring mode (PMRM) proved superior to the classic single quadrupole technique, with enhanced sensitivity and more accurate. Trace level PAHs could be readily confirmed by their retention times and characteristic ions. The concentrations of PAHs in these cigarette samples ranged from 455.9ng/cig to 1201.3ng/cig in the range of cigarette tar between 5mg and 12mg, with the main components being two-, three, and four-ring PAHs. When tar is over 10mg, there is 14.4% increase in PAH concentrations on average than that tar is between 8 and 10mg, while there is 28.6% decrease when tar is below 6mg. These results indicate that relative low-tar cigarettes provide relative low emission levels of PAHs.

A Novel Indicator of Life-Course Smoking Prevalence in the United States Combining Popularity, Duration, Quantity, and Quality of Smoking.

To develop a smoking indicator that combines the popularity and duration of smoking and the quantity and quality of consumed cigarettes, factors that vary dramatically over time and across generations. We used retrospective reports on smoking behavior and a time series of cigarette tar yields to standardize nationally representative life-course smoking prevalence rates of 11 generations of US men and women, spanning 120 years. For each generation and gender, we related the standardized data with the corresponding rates of smoking-attributable mortality. Our indicator suggests that US cigarette consumption spread, peaked, and contracted faster than commonly perceived; predicts a significantly stronger smoking-mortality correlation than unadjusted smoking prevalence; and reveals the emergence of a delay (by up to 8 years) in premature death from smoking that is consistent with increasing population access to effective treatments. In fact, we show that, among recent cohorts, smoking health-risk exposure is at a historic low and will account for less than 5% of deaths. Relative to unstandardized measures, our novel, standardized indicator of smoking prevalence describes a different history of smoking diffusion in the United States, and more strongly predicts later-life mortality.