The effect of cotinine or cigarette smoke co-administration on the formation of O6-methylguanine adducts in the lung and liver of A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
(1/2289)
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific nitrosamine, induces lung adenomas in A/J mice, following a single intraperitoneal (i.p.) injection. However, inhalation of tobacco smoke has not induced or promoted tumors in these mice. NNK-induced lung tumorigenesis is thought to involve O6-methylguanine (O6MeG) formation, leading to GC-->AT transitional mispairing and an activation of the K-ras proto-oncogene in the A/J mouse. NNK can be metabolized by several different cytochromes P450, resulting in a number of metabolites. Formation of the promutagenic DNA adduct O6MeG is believed to require metabolic activation of NNK by cytochrome P450-mediated alpha-hydroxylation of the methylene group adjacent to the N-nitroso nitrogen to yield the unstable intermediate, methanediazohydroxide. Nicotine, cotinine (the major metabolite of nicotine), and aqueous cigarette tar extract (ACTE) have all been shown to effectively inhibit metabolic activation of NNK to its mutagenic form, most likely due to competitive inhibition of the cytochrome P450 enzymes involved in alpha-hydroxylation of NNK. The objective of the current study was to monitor the effects of cotinine and cigarette smoke (CS) on the formation of O6MeG in target tissues of mice during the acute phase of NNK treatment. To test the effect of cotinine, mature female A/J mice received a single intraperitoneal injection of NNK (0, 2.5, 5, 7.5, or 10 mumole/mouse) with cotinine administered at a total dose of 50 mumole/mouse in 3 separate i.p. injections, administered 30 min before, immediately after, and 30 min after NNK treatment. To test the effect of whole smoke exposure on NNK-related O6MeG formation, mice were exposed to smoke generated from Kentucky 1R4F reference cigarettes at 0, 0.4, 0.6, or 0.8 mg wet total particulate matter/liter (WTPM/L) for 2 h, with a single i.p. injection of NNK (0, 3.75, or 7.5 mumole/mouse) midway through the exposure. Cigarette smoke alone failed to yield detectable levels of O6MeG. The number of O6MeG adducts following i.p. injection of NNK was significantly (p < 0.05) reduced in both lung and liver by cotinine and by cigarette smoke exposure. Our results demonstrate that NNK-induced O6MeG DNA adducts in A/J mice are significantly reduced when NNK is administered together with either cotinine, the major metabolite of nicotine, or the parental complex mixture, cigarette smoke. (+info)
Evaluation of passive smoking by measuring urinary trans, trans-muconic acid and exhaled carbon monoxide levels.
(2/2289)
No method has yet been established to evaluate the exposure to tobacco smoke in passive smoking (PS). We therefore conducted a study on the possibility that the levels of urinary trans, trans-muconic acid (MA) and the exhaled carbon monoxide (CO) could be indices of the passive exposure to tobacco smoke. The moderate correlation was observed between urinary MA levels and the number of consumed cigarettes per day in smokers. The mean urinary MA level of the PS (+) group was significantly higher than that with the PS (-) group. Among the PS (+) group, the mean MA level in the urine obtained in the afternoon was higher than that obtained in the morning. A high correlation was observed between the exhaled CO levels and the number of consumed cigarettes per day in smokers. Like the urinary MA level, the mean exhaled CO level in the PS (+) group, too, gave a significantly higher level than in the PS (-) group. Because the biological half life of MA (7.5 +/- 0.85 h) was longer than that of CO (3.0 +/- 0.36 h), the measurement of urinary MA level is recommended for evaluating the exposure of passive smoking. The measurement of exhaled CO levels is useful only for chain smokers and nonsmokers with PS just before measurement. (+info)
The role of domestic factors and day-care attendance on lung function of primary school children.
(3/2289)
The results of studies examining the relationship of domestic factors to lung function are contradictory. We therefore examined the independent effects of maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), the presence of a cat, type of heating and cooking used in the home and day-care attendance on lung function after controlling for socioeconomic status (SES). Nine hundred and eighty-nine children from 18 Montreal schools were studied between April 1990 and November 1992. Information on the child's health and exposure to domestic factors was collected by questionnaire. Spirometry was performed at school. The data were analysed by multiple linear regression with percent predicted FEV1, FVC, and FEV1/FVC as dependent variables. In the overall sample (both sexes combined), cat in the home (regression coefficient, beta = -1.15, 95% confidence interval, CI: -2.26-(-)0.05) and electric baseboard units (beta = -1.26, 95% CI: -2.39-(-)0.13) were independently associated with a lower FEV1/FVC, while day-care attendance (beta = -2.05, 95% CI: -3.71-(-)0.40) significantly reduced FEV1. Household ETS was significantly associated with increasing level of FVC (beta = 2.86, 95% CI: +0.55 to +5.17). In boys but not girls, household ETS (beta = -2.13, 95% CI: -4.07-(-)0.19) and the presence of a cat (beta = -2.19, 95% CI: -3.94-(-)0.45) were associated with lower FEV1/FVC. By contrast, day-care attendance was associated with lower FEV1 (beta = -2.92, 95% CI: -5.27-(-)0.56) and FEV1/FVC (beta = -1.53, 95% CI: -2.73-(-)0.33) in girls only. In conclusion, the results provide evidence that domestic factors and day-care attendance primarily affected airway caliber and gender differences were apparent in the effects of these factors. (+info)
Passive smoking and the risk of coronary heart disease--a meta-analysis of epidemiologic studies.
(4/2289)
BACKGROUND: The effect of passive smoking on the risk of coronary heart disease is controversial. We conducted a meta-analysis of the risk of coronary heart disease associated with passive smoking among nonsmokers. METHODS: We searched the Medline and Dissertation Abstracts Online data bases and reviewed citations in relevant articles to identify 18 epidemiologic (10 cohort and 8 case-control) studies that met prestated inclusion criteria. Information on the designs of the studies, the characteristics of the study subjects, exposure and outcome measures, control for potential confounding factors, and risk estimates was abstracted independently by three investigators using a standardized protocol. RESULTS: Overall, nonsmokers exposed to environmental smoke had a relative risk of coronary heart disease of 1.25 (95 percent confidence interval, 1.17 to 1.32) as compared with nonsmokers not exposed to smoke. Passive smoking was consistently associated with an increased relative risk of coronary heart disease in cohort studies (relative risk, 1.21; 95 percent confidence interval, 1.14 to 1.30), in case-control studies (relative risk, 1.51; 95 percent confidence interval, 1.26 to 1.81), in men (relative risk, 1.22; 95 percent confidence interval, 1.10 to 1.35), in women (relative risk, 1.24; 95 percent confidence interval, 1.15 to 1.34), and in those exposed to smoking at home (relative risk, 1.17; 95 percent confidence interval, 1.11 to 1.24) or in the workplace (relative risk, 1.11; 95 percent confidence interval, 1.00 to 1.23). A significant dose-response relation was identified, with respective relative risks of 1.23 and 1.31 for nonsmokers who were exposed to the smoke of 1 to 19 cigarettes per day and those who were exposed to the smoke of 20 or more cigarettes per day, as compared with nonsmokers not exposed to smoke (P=0.006 for linear trend). CONCLUSIONS: Passive smoking is associated with a small increase in the risk of coronary heart disease. Given the high prevalence of cigarette smoking, the public health consequences of passive smoking with regard to coronary heart disease may be important. (+info)
One study after another is finding strong associations between a variety of human illness and exposure to environmental tobacco smoke (ETS). A 1986 report by the U.S. Surgeon General concluded that ETS is a cause of disease, including lung cancer, in healthy nonsmokers. Other reports have documented causal associations between ETS and lower respiratory tract infections, middle ear disease and exacerbation of asthma in children, heart disease, retardation of fetal growth, sudden infant death syndrome, and nasal sinus cancer. However, the findings from many of these studies remain controversial. A number of scientists remain skeptical about the association between ETS and serious illness in nonsmokers, charging that scientific journals either fail to publish pro-tobacco findings and meta-analyses or disregard those that are published. They also claim that many epidemiological studies declare causal associations based on marginal odds ratios. (+info)
Health effects of passive smoking-10: Summary of effects of parental smoking on the respiratory health of children and implications for research.
(6/2289)
BACKGROUND: Two recent reviews have assessed the effect of parental smoking on respiratory disease in children. METHODS: The results of the systematic quantitative review published as a series in Thorax are summarised and brought up to date by considering papers appearing on Embase or Medline up to June 1998. The findings are compared with those of the review published recently by the Californian Environmental Protection Agency (EPA). Areas requiring further research are identified. RESULTS: Overall there is a very consistent picture with odds ratios for respiratory illnesses and symptoms and middle ear disease of between 1.2 and 1.6 for either parent smoking, the odds usually being higher in pre-school than in school aged children. For sudden infant death syndrome the odds ratio for maternal smoking is about 2. Significant effects from paternal smoking suggest a role for postnatal exposure to environmental tobacco smoke. Recent publications do not lead us to alter the conclusions of our earlier reviews. While essentially narrative rather than systematic and quantitative, the findings of the Californian EPA review are broadly similar. In addition they have reviewed studies of the effects of environmental tobacco smoke on children with cystic fibrosis and conclude from the limited evidence that there is a strong case for a relationship between parental smoking and admissions to hospital. They also review data from adults of the effects of acute exposure to environmental tobacco smoke under laboratory conditions which suggest acute effects on spirometric parameters rather than on bronchial hyperresponsiveness. It seems likely that such effects are also present in children. CONCLUSIONS: Substantial benefits to children would arise if parents stopped smoking after birth, even if the mother smoked during pregnancy. Policies need to be developed which reduce smoking amongst parents and protect infants and young children from exposure to environmental tobacco smoke. The weight of evidence is such that new prevalence studies are no longer justified. What are needed are studies which allow comparison of the effects of critical periods of exposure to cigarette smoke, particularly in utero, early infancy, and later childhood. Where longitudinal studies are carried out they should be analysed to look at the way in which changes in exposure are related to changes in outcome. Better still would be studies demonstrating reversibility of adverse effects, especially in asthmatic subjects or children with cystic fibrosis. (+info)
Urinary cotinine and exposure to parental smoking in a population of children with asthma.
(7/2289)
BACKGROUND: Studies of the effects of tobacco smoke often rely on reported exposure to cigarette smoke, a measure that is subject to bias. We describe here the relationship between parental smoking exposure as assessed by urinary cotinine excretion and lung function in children with asthma. METHODS: We studied 90 children 4-14 years of age, who reported a confirmed diagnosis or symptoms of asthma. In each child, we assessed baseline pulmonary function (spirometry) and bronchial responsiveness to carbachol stimulation. Urinary cotinine was measured by HPLC with ultraviolet detection. RESULTS: Urinary cotinine concentrations in the children were significantly correlated (P <0.001) with the number of cigarettes the parents, especially the mothers, smoked. Bronchial responsiveness to carbachol (but not spirometry test results) was correlated (P <0.03) with urinary cotinine in the children. CONCLUSION: Passive smoke exposure increases the bronchial responsiveness to carbachol in asthmatic children. (+info)
Ischemic stroke risk and passive exposure to spouses' cigarette smoking. Melbourne Stroke Risk Factor Study (MERFS) Group.
(8/2289)
OBJECTIVES: This study investigated the association between ischemic stroke risk and passive exposure to cigarette smoking. METHODS: Risk factors among 452 hospitalized cases of first-episode ischemic stroke were compared with 452 age- and sex-matched "neighbor-hood" controls. RESULTS: The risk of stroke was twice as high for subjects whose spouses smoked as for those whose spouses did not smoke (95% confidence interval = 1.3, 3.1), after adjustment for the subject's own smoking, heart disease, hypertension, diabetes, and education level. These results were confirmed when analysis was limited to those who never smoked. CONCLUSIONS: These findings provide evidence that spousal smoking may be a significant risk factor for ischemic stroke. (+info)