Significance of exposure to sidestream tobacco smoke

The presence of toxins and carcinogens in ambient air polluted with tobacco smoke is largely due to the sidestream smoke emissions from the smouldering tobacco products. Levels of these toxins and carcinogens in sidestream smoke often exceed their concentrations in mainstream smoke. Dosimetry of tobacco-specific markers of exposure in physiologic fluids suggests that in regard to nicotine--which is the major tobacco alkaloid--exposure of humans to environmental tobacco smoke causes but a few percent of the nicotine levels reached as a result of active inhalation of cigarette mainstream smoke. Yet, this measurement of exposure is not universally applicable to all of the tobacco smoke pollutants in this complex matrix. Existing knowledge of the chemical composition of sidestream smoke and evidence of biological activity of sidestream smoke components suggests that this environmental pollutant has carcinogenic potential. Significance of exposure to environmental tobacco smoke must be evaluated on the basis of the severity of the pollution, the duration of exposure and personal variations in uptake.     

Epidemiology of environmental tobacco smoke exposure

The health hazards due to exposure to environmental tobacco smoke (ETS) are increasingly established. ETS contains thousands of chemicals including 43 known carcinogens. One of the most important known health effects of ETS exposure is lung cancer in non-smokers, based on epidemiologic evidence and knowledge of the uptake and metabolism of ETS. Epidemiologic studies need to carefully take into account confounding and potential errors in exposure assessment. More research is needed to understand the genetic factors that influence ETS-induced lung cancer. Studies of the patterns of ETS exposure suggest higher rates of exposure in people employed as blue collar workers, in service occupations, earning lower incomes, and among the less educated. Certain racial/ethnic groups (e.g. Blacks, American Indians) may be at higher risk of ETS exposure. Despite substantial progress in protecting individuals from ETS exposure, additional efforts are needed in improving and enforcing policies to reduce exposure.     

Lifetime tobacco smoke exposure and breast cancer incidence

Purpose  

We analyzed data from a case–control study to assess the association between lifetime tobacco smoke exposure and breast cancer incidence.     

Assessment of the carcinogenic N-nitrosodiethanolamine in tobacco products and tobacco smoke

A simple, reproducible gas chromatography-thermal energy analyzer(g.c.-TEA) method has been developed for the analysis of N-nitrosodiethanolainlne(NDELA) in tobacco and tobacco smoke. The extract of tobaccoor the trapped particulates of tobacco smoke are chromatographedon silica gel. The NDELA containing fractions are concentrated,silylated and analyzed with a modified g.c.-TEA system. [¹⁴C]NDELAserves as internal standard for the quantitative analysis. Experimentalcigarettes made from tobaccos which were treated with the suckergrowth inhibitor maleic hydrazide-diethanolamlne (MH-DELA) contained115–420 p.p.b. of NDELA and their smoke contained 20–290ng/cigarette, whereas hand-suckered tobacco and its smoke werefree of NDELA. The tobacco of US smoking products contained115–420 p.p.b. of NDELA and the mainstream smoke fromsuch products yielded 10–68 ng/cigar or cigarette. NDELAlevels in chewing tobacco ranged from 220–280 p.p.b. andin two commercial snuff products were 3,200 and 6,800 p.p.b.Although the five analyzed MH-DELA preparations contained between0.6–1.9 p.p.m. NDELA it is evident that the major portionof NDELA in tobacco is formed from the DELA residue during thetobacco processing. Based on bioassay data from various laboratorieswhich have shown that NDELA is a relatively strong car cinogenand based on the results of this study the use of MH-DELA forthe cultivation of tobacco is questioned.     

Breast cancer and exposure to tobacco smoke during potential windows of susceptibility

Purpose

An association between smoking and breast cancer is unresolved, although a higher risk from exposure during windows of susceptibility has been proposed. The objective of this prospective study was to evaluate the association between tobacco smoke and breast cancer with a focus on timing of exposure, especially during early life.

Methods

Sister study participants (n = 50,884) aged 35–74 were enrolled from 2003 to 2009. Women in the United States and Puerto Rico were eligible if they were breast cancer-free but had a sister with breast cancer. Participants completed questionnaires on smoking and environmental tobacco smoke (ETS) exposure. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk.

Results

During follow-up (mean = 6.4 years), 1,843 invasive breast cancers were diagnosed. Neither active smoking nor adult ETS was associated with breast cancer risk. However, never smoking women exposed to ETS throughout their childhood had a 17% higher risk of breast cancer (95% CI 1.00–1.36) relative to those with no exposure. In utero ETS exposure was also associated with breast cancer (HR = 1.16, 95% CI 1.01–1.32) and the HR was most elevated for women born in earlier birth cohorts (<1940, HR = 1.44, 95% CI 1.02–2.02; 1940–1949, HR = 1.28, 95% CI 1.01–1.62).

Conclusion

In utero ETS and ETS exposure during childhood and adolescence were associated with increased risk of breast cancer and associations varied by birth cohort.

     

Determinants of exposure to environmental tobacco smoke in 21,588 Italian non-smokers

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is associated with an increased risk of lung cancer, ischemic heart disease and respiratory diseases in non-smokers. Exposure is likely to be uneven in the population. Knowledge of its distribution is important for a better planning of preventive activities. METHODS: In the context of the Italian branch of the EPIC prospective investigation, in which we enrolled 47,000 volunteers, we have surveyed exposure to ETS and its determinants (age, social class, occupation). The purpose of the present paper is to contribute to identify the main sources of exposure in Italy. RESULTS: We found, in a sample of 21,588 Italian non-smokers, a prevalence of 0.337 (95% confidence interval, 0.336-0.337) in women and 0.537 (0.529-0.544) in men. Exposure was defined as at least 1 hr/day for at least one year. Exposure at work is by far the commonest source of exposure to ETS, with a strong difference between full-time and part-time jobs. The distribution of exposure by social class was uneven, with statistically significant odds ratios for higher social groups in the order of 0.4-0.5. White-collar workers are the occupational category mostly exposed, suggesting that the implementation of anti-smoking legislation is still incomplete in Italian offices. CONCLUSIONS: The uneven distribution of ETS in the population is a matter of concern, since it contributes to the unequal distribution of health in different social groups.     

Dietary patterns of female nonsmokers with and without exposure to environmental tobacco smoke

The relationship of passive smoking to diet was examined in 82 female nonsmokers who provided a quantitative diet history in 1986. Exposure to environmental tobacco smoke (ETS) was assessed by urinary cotinine measurement. Mean values for each dietary variable, adjusted for age, ethnicity, education, and last week's ethanol intake, were compared among unexposed women and women with low or high ETS exposure. Linear relationships with amount of ETS exposure were also sought. Intakes of beta-carotene and cholesterol were found to be inversely related to ETS exposure. Since these nutrients have been associated with lung cancer risk, they are potential confounders of the passive-smoking/lung-cancer relationship. Although we estimate the confounding effect of these dietary factors to be modest, they should be measured carefully in future studies of this relationship.This work was supported in part by Public Health Service grant CA-33619 from the National Cancer Institute, and the International Agency for Research on Cancer.     

DNA and protein adducts in human tissues resulting from exposure to tobacco smoke

Tobacco smoke contains a variety of genotoxic carcinogens that form adducts with DNA and protein in the tissues of smokers. Not only are these biochemical events relevant to the carcinogenic process, but the detection of adducts provides a means of monitoring exposure to tobacco smoke. Characterization of smoking-related adducts has shed light on the mechanisms of smoking-related diseases and many different types of smoking-derived DNA and protein adducts have been identified. Such approaches also reveal the potential harm of environmental tobacco smoke (ETS) to nonsmokers, infants and children. Because the majority of tobacco-smoke carcinogens are not exclusive to this source of exposure, studies comparing smokers and nonsmokers may be confounded by other environmental sources. Nevertheless, certain DNA and protein adducts have been validated as biomarkers of exposure to tobacco smoke, with continuing applications in the study of ETS exposures, cancer prevention and tobacco product legislation. Our article is a review of the literature on smoking-related adducts in human tissues published since 2002.     

Active and passive cigarette smoke exposure and cervical intraepithelial neoplasia.

This case-control analysis presents odds ratios for active and passive cigarette smoke exposure and cervical intraepithelial neoplasia of levels II and III (CIN II and CIN III) while controlling for confounders. From 1987 to 1988, 103 biopsy-conformed incident cases of CIN II or III and 268 controls with normal cervical cytology were enrolled. Seventy % of cases were cigarette smokers, while only 30% of controls had ever smoked. The adjusted odds ratio for current cigarette smoking was 3.4 (95% confidence interval, 1.7-7.0). The following confounders were included in logistic regression models: age, race, education, number of sex partners, contraceptive use, sexually transmitted disease history, and Pap smear history. The risk of CIN II/III increased with increasing years of cigarette smoking and with increasing pack-years of exposure. Smoking was associated more strongly with CIN III than CIN II. The effect of passive cigarette smoke exposure was explored separately for smokers and nonsmokers and was found not to be consistently associated with CIN II/III when controlling for confounders.     

Urinary excretion of 3-methyladenine and 3-ethyladenine after controlled exposure to tobacco smoke

The urinary excretion of the DNA alkylation products 3-methyladenine(3-MeAde) and 3-ethyladenine (3-EtAde) after controlled exposureto cigarette smoke over a period of 4 days was determined bycompetitive radioimmunoassay after separation by HPLC. Twenty-fourhour urine samples were collected from five smokers and fivenon-smokers. Days 1 and 3 (control days) were without smoking,on days 2 and 4 smokers consumed 24 cigarettes each within 8h in an unventilated room (45 m³) in the presence of non-smokers.Average levels of carbon monoxide during exposure were 15–20p.p.m., 2.8–3.5 mg/m³ of respirable suspended particlesand 75–86 µg/m³ of nicotine. Carboxy-hemoglobinlevels increased by 9.0 and 1.8% in smokers and passive smokersrespectively. On control days, urinary excretion of 3-MeAdewas similar in smokers and non-smokers (4.7–6.2 µg/24h). Smoking resulted in a significant increase (P < 0.01)in 3-MeAde excretion (13.6–14.8 µg/24 h); no changewas observed in the average excretion of 3-MeAde by passivesmokers (4.8–4.9 ug of 3-MeAde/24 h). Baseline 3-EtAdeexcretion on control days was similar in smokers and passivesmokers (13.7–32.8 ng/ 24 h). In smokers, the amount ofurinary 3-EtAde was increased >5-fold (119.3–138.5ng/24 h) on smoking days; no effect on 3-EtAde excretion wasobserved on average in passive smokers (18.0–25.2 ng/24h). The nature of the DNA-reactive agent(s) responsible forthe increased urinary excretion of 3-alkyladenines, in particularof the sensitive indicator 3-EtAde, remains to be determined.     

A molecular dosimetry approach to assess human exposure to environmental tobacco smoke in pubs

Although the involvement of environmental tobacco smoke (ETS) in human lung cancer is no longer a matter of dispute, the magnitude of its impact still is. This is mainly due to the inefficiency of methodology to assess exposure to ETS especially in public places. Setting a real life exposure condition (3 h stay in local pubs) and using a matched-control study design, we quantified smoke-related DNA adducts in induced sputum and peripheral blood lymphocytes (PBL) of healthy non-smokers (n = 15) before and after a single pub visit by means of the (32)P-post-labeling assay. For verification, we also measured a spectrum of polycyclic aromatic hydrocarbons (PAH) in the ambient air of the pubs by personal air monitors, and determined the plasma concentrations of nicotine and cotinine by gas chromatography/mass spectrometry. The ambient air concentrations of all PAH were several orders of magnitude higher than those already reported for other indoor environments. The plasma concentrations of both nicotine and cotinine increased significantly after the pub visit (P = 0.001 and P = 0.0007, respectively). Accordingly, the overall DNA adduct profile in induced sputum, but not in PBL, changed quantitatively and qualitatively after the pub visit. Of most significance was the formation of a distinct DNA adduct in induced sputum of three individuals consequent to ETS exposure. This adduct co-migrated with the standard (+/-)-anti-benzo[a]pyrene diol epoxide-DNA adduct, which is known to form at lung cancer mutational hotspots. We conclude that real life exposure to ETS can give rise to pro-mutagenic lesions in the lower airway, and this can be best investigated in a relevant surrogate matrix such as induced sputum.     

Toenail nicotine levels as a biomarker of tobacco smoke exposure.

Currently used biomarkers of tobacco smoke exposure have several disadvantages, including that they reflect short-term exposure and can therefore be affected by day-to-day variations. The aim of this study was to assess the validity of toenail nicotine levels as a biomarker of exposure to tobacco smoke for use in epidemiological studies. Toenails were collected in 1982 from 62,641 women participating in the Nurses' Health Study, whereas questionnaire data at that time provided information on active and passive smoke exposure. A stratified random sample of stored toenails from 106 women were selected according to their reported exposure category. Toenails were analyzed for nicotine levels by high-performance liquid chromatography. Toenail nicotine levels differed significantly according to tobacco smoke exposure (P < 0.0001). Among nonactive smokers, there was a significant difference in toenail nicotine levels between passive smokers (mean = 0.28 ng/mg) and nonexposed women (mean = 0.08 ng/mg; P = 0.0006). Among active smokers, there was also a significant difference (P = 0.04) in mean nicotine levels according to categories of cigarettes smoked (means for smokers of 1-14, 15-24, and 25 or more cigarettes/day were 0.94, 1.81, and 2.40 ng/mg). An overlap of the distribution of nicotine levels among passive and active smokers was found. Among all women, the correlation between nail nicotine levels and smoking exposure categories was r = 0.80 (P < 0.0001). The results of this study indicate that toenail nicotine level measurement is a valid biomarker for assessment of active and passive exposure to tobacco smoke. Nail nicotine levels may reflect aspects of active and passive exposure not captured by standard questionnaires and, thus, have the potential to provide better assessment of associations with health risk.     

Factors modifying exposure to environmental tobacco smoke in children (Athens, Greece)

The aim of the study was to investigate individual, family, and environmental factors which may modify exposure of children to environmental tobacco smoke (ETS). A total of 2,108 children of both genders, aged up to 14 years old, were enrolled in the study. Parents of the children provided information concerning several factors that may affect exposure to ETS. Cotinine-to-creatinine ratios in spot urine samples were measured for each child. These values were logtransformed and regressed on a series of exposure variables. Among children, 73 percent were exposed to ETS generated by at least one smoker in the household. Exposure to ETS was affected by the following factors: cigarettes smoked by parents while the child was at home (increase by 37 percent per 10 cigarettes daily, 95 percent confidence interval [CI]=32-43 percent); precautions taken by parents (no cf yes, increase by 38 percent, CI=24-54 percent); child's age (decrease by nine percent per year, CI=-11--8 percent); gender (male lower than female by 13 percent, CI=-21--3 percent); day of the week (Monday cf Tuesday-through-Sunday, increase by 28 percent, CI=14-44 percent); floor surface area (decrease by nine percent per 20m2, CI=-14--5 percent); heating (central cf non-central decrease by 14 percent, CI=-25--2 percent); maternal education (decrease by nine percent per five years, CI=-18-0 percent); paternal education (decrease by seven percent per five years, CI=-15-2 percent). It is concluded that several household-related factors affect exposure to ETS and that this exposure can be reduced by about one-third by simple precautions taken by smoking parents.     

Parent-reported environmental tobacco smoke exposure among preadolescents and adolescents treated for cancer

Exposure to environmental tobacco smoke (ETS) poses serious health risks for children with cancer. Parental smoke is a primary source of exposure for these children. Parent smoking behaviors and parent-reported ETS exposure among children treated for cancer were examined in this study. In addition, reports of ETS exposure among children with cancer who currently smoked or who had smoked in the past were compared to those of children with cancer who never smoked. Written questionnaires about smoking behaviors and ETS exposure were administered to 47 smoking parents of youngsters diagnosed with cancer, 10-18 years of age (57.4% male, 78.7% Caucasian). Child reports of smoking status were also obtained. Results indicated that children with cancer are exposed to ETS from a number of sources and settings, as reported by their parents. Current or previous child smokers had greater ETS exposure than non-smoking children. Older children and Caucasian children also had greater ETS exposure. Level of ETS exposure did not differ based on the child's treatment status. Interventions that teach parents to protect their youngster from ETS exposure have potential for reducing adverse health outcomes in this vulnerable population.     

Biologic damage resulting from exposure to tobacco smoke and from radon: implication for preventive interventions

Cigarette smoking and residential radon are, respectively, the first and second leading cause of lung cancer in the United States today. Of the approximately 157 000 lung deaths occurring in 2000, approximately 90% can be attributed to cigarette smoking and 30% of the lung cancer deaths among non-smokers can be attributed to residential radon exposure. Although dwarfed by cigarette related lung cancer, lung cancer among lifetime non-smokers is a leading cause of death in the United States, and many other countries, accounting for approximately 16 000 deaths per year in the US. Laboratory studies and epidemiological investigations, particularly those conducted in the past decade, are yielding evidence that tobacco smoke and radon may share important elements of lung cancer's pathologic mechanism(s). Lung cancer prevention among smokers, ex-smokers and lifetime nonsmokers can be enhanced as we learn more about the etiologic mechanism(s) of lung cancer resulting from these and other exposures including diet, non-malignant respiratory diseases, occupational exposures, and susceptibility-gene. In this article we review both laboratory and epidemiologic data that gives insight into the biologic damage done to the lung from these exposures.