Rat pleural mesothelial cells show damage after exposure to external but not internal cigarette smoke.

The combination of cigarette smoke and high-level occupational asbestos exposure produces a synergistic increase in the incidence of lung cancer; however, smoking does not affect the incidence of mesothelioma. Here we present the results of tests of two theories that have been proposed to explain this phenomenon; namely, that pleural mesothelial cells are resistant to cigarette smoke-induced damage and that the pleural connective tissue acts as a barrier that prevents smoke from reaching the mesothelial cells. To test these hypotheses, excised whole rat lung preparations were exposed to either internal (intratracheal) or external (pleural surface) smoke. For comparison, additional excised lung preparations were exposed to solutions of hydrogen peroxide either externally or intratracheally. Mesothelial cells exposed to external smoke showed widespread, dose-dependent uptake of Trypan blue. Mesothelial cells did not take up Trypan blue after exposure to internal smoke. Bronchial epithelial cells exposed to internal smoke did show uptake, but to a lesser degree than externally exposed mesothelial cells. Examination by scanning and transmission electron microscopy showed that internal smoke did not affect mesothelial cell ultrastructure, whereas external smoke produced obvious mesothelial cell damage and mesothelial cell detachment. Catalase and deferoxamine, scavengers of active oxygen species, provided protection against smoke-induced mesothelial cell injury, but inactivated catalase did not. External hydrogen peroxide produced a very similar, dose-dependent pattern of Trypan blue uptake and ultrastructural changes. Intratracheal hydrogen peroxide also damaged mesothelial cells, but the extent of damage was always less than with comparable concentrations of external hydrogen peroxide.(ABSTRACT TRUNCATED AT 250 WORDS)     

香烟烟雾对雄性小鼠睾丸细胞DNA损伤的研究

分别以二甲基亚砜 (DMSO)和磷酸缓冲液 (PBS)作为吸收液 ,用大气收集器 (U形多孔玻板吸收管 )采集香烟主流烟雾 ,制得 DMSO烟雾溶液和 PBS烟雾溶液。用彗星试验检测了这 2种烟雾溶液对小鼠睾丸细胞的 DNA损伤作用。结果显示 :2种烟雾溶液均含有 DNA损伤剂 ,可引起小鼠睾丸细胞的 DNA损伤 ,且 DMSO烟雾溶液的细胞毒性和遗传毒性均明显高于 PBS烟雾溶液。该研究为香烟的雄性生殖毒性评价提供了理论依据 ,同时也为香烟的研究提供了更为方便的手段。     

Increasing selenium in cigarettes and smoke: transfer to smoke

The selenium content of some American tobaccos and cigarettes was determined. The quantities of added selenium that were transferred from cigarettes to inhaled, mainstream smoke were examined for several commercial and experimental cigarettes of different tar levels. For high-tar cigarettes, as much as 10% of added selenium was found in mainstream smoke, while low-tar cigarettes delivered about 3% of added selenium. Transfer rates of selenium to mainstream smoke are reported for various levels of fortification (0-25 micrograms/cigarette) and the rationale for selenium fortification is discussed. Based on highly favorable reports in the literature on the antitumor activity of selenium, the fortification of tobacco with selenium may become a viable way of producing a safer tobacco product. It is proposed that such selenium-fortified smoking products be developed and evaluated extensively.     

White blood cell DNA adducts in a cohort of asthmatic children exposed to environmental tobacco smoke

Purpose  

Exposure to environmental tobacco smoke (ETS) leads to molecular damage in the form of DNA adducts. While lung cancer risk is higher among African Americans compared to White Americans, a few studies have tested for racial differences in DNA adducts among children exposed to ETS. The purpose of this study was to test whether African American children have higher DNA adducts levels compared to White children adjusted for ETS exposure.     

Perinatal environmental tobacco smoke exposure in rhesus monkeys: critical periods and regional selectivity for effects on brain cell development and lipid peroxidation

Perinatal environmental tobacco smoke (ETS) exposure in humans elicits neurobehavioral deficits. We exposed rhesus monkeys to ETS during gestation and through 13 months postnatally, or postnatally only (6-13 months). At the conclusion of exposure, we examined cerebrocortical regions and the midbrain for cell damage markers and lipid peroxidation. For perinatal ETS, two archetypal patterns were seen in the various regions, one characterized by cell loss (reduced DNA concentration) and corresponding increases in cell size (increased protein/DNA ratio), and a second pattern suggesting replacement of larger neuronal cells with smaller and more numerous glia (increased DNA concentration, decreased protein/DNA ratio). The membrane/total protein ratio, a biomarker of neurite formation, also indicated potential damage to neuronal projections, accompanied by reactive sprouting. When ETS exposure was restricted to the postnatal period, the effects were similar in regional selectivity, direction, and magnitude. These patterns resemble the effects of prenatal nicotine exposure in rodent and primate models. Surprisingly, perinatal ETS exposure reduced the level of lipid peroxidation as assessed by the concentration of thiobarbituric acid reactive species, whereas postnatal ETS did not. The heart, a tissue that, like the brain, has high oxygen demand, displayed a similar but earlier decrease (2-3 months) in lipid peroxidation in the perinatal exposure model, whereas values were reduced at 13 months with the postnatal exposure paradigm. Our results provide a mechanistic connection between perinatal ETS exposure and neurobehavioral anomalies, reinforce the role of nicotine in these effects, and buttress the importance of restricting or eliminating ETS exposure in young children.     

Yields of tar, nicotine, and carbon monoxide in the sidestream smoke from 15 brands of Canadian cigarettes

Sidestream smoke yields for 15 brands of cigarettes were determined under conditions where mainstream yields were approximately equal to those used for determining the values which appear on packages of Canadian cigarettes. Sidestream yields of tar, nicotine, and carbon monoxide were much higher than mainstream yields for all brands tested. The average sidestream-to-mainstream ratios for the 15 brands were 3.5, 6.6, and 6.8 for tar, nicotine, and carbon monoxide, respectively. The highest yields of sidestream were obtained from the brands with the lowest mainstream yields.     

Importance of exposure to gaseous and particulate phase components of tobacco smoke in active and passive smokers

Summary The uptake of tobacco smoke constituents from gaseous and particulate phases of mainstream smoke (MS), inhaled by smokers, and of environmental tobacco smoke (ETS), breathed in by non-smokers, was investigated in two experimental studies. Tobacco smoke uptake was quantified by measuring carboxyhemoglobin (COHb), nicotine and cotinine in plasma and urine and the data obtained were correlated with urinary excretion of thioethers and of mutagenic activity. An increase in all biochemical parameters was observed in smokers inhaling the complete MS of 24 cigarettes during 8 h, whereas only an increase in COHb and, to a minor degree, in urinary thioethers was found after smoking the gas phase of MS under similar conditions. Exposure of non-smokers to the gaseous phase of ETS or to whole ETS at similar high concentrations for 8 h led to identical increases in COM, plasma nicotine and cotinine as well as urinary excretion of nicotine and thioethers which were much lower than in smokers. Urinary mutagenicity was not found to be elevated under either ETS exposure condition. As shown by our results, the biomarkers most frequently used for uptake of tobacco smoke (nicotine and cotinine) indicate on the one hand the exposure to particulate phase constituents in smoking but on the other hand the exposure to gaseous phase constituents in passive smoking. Particle exposure during passive smoking seems to be low and a biomarker which indicates ETS particle exposure is as yet not available. These findings emphasize that risk extrapolations from active smoking to passive smoking which are based on cigarette equivalents or the use of one biomarker (e.g. cotinine) might be misleading.     

A study on the mutagenicity of tobacco smoke from low-tar cigarettes

A series of 16 low-tar cigarettes, yielding from 1 to 10 mg of tar, were smoked on a modified cigarette smoking machine that collected both mainstream (MS, inhaled) smoke and sidestream (SS, between puffs) smoke. The SS smoke is the major contributor to environmental tobacco smoke. The collected MS and SS smoke condensates were evaluated for mutagenicity by the Ames test and compared with MS and SS smoke condensates from a high-tar cigarette. Both MS and SS condensates of low-tar cigarettes (LTCs) were tested with the Salmonella strains TA1538 and TA100. Except for three cigarettes, the MS smoke mutagenicities of the LTC smoke condensates were significantly reduced (about 30%) when compared with a control, high-tar (23-mg) cigarette. Opposite results were obtained for the SS smoke condensates, which were more mutagenic (about 20%) than the SS smoke condensate of the high-tar cigarette. Thus, LTC mainstream smoke may be less hazardous to the LTC smoker, whereas LTC sidestream may emit more mutagenic compounds into environmental tobacco smoke, which, through passive inhalation, could affect both smokers and nonsmokers.     

Inhalation of hazardous air pollutants from environmental tobacco smoke in US residences

In the United States, 48 million adults smoke 3.5-5 x 10(11) cigarettes/year. Many cigarettes are smoked in private residences, causing regular environmental tobacco smoke (ETS) exposure to roughly 31 million nonsmokers (11% of the US population), including 16 million juveniles. (Upper bound estimates are 53 million exposed nonsmokers including 28 million juveniles.) ETS contains many chemical species whose industrial emissions are regulated by the US federal government as hazardous air pollutants (HAPs). In this paper, average daily residential exposures to and intakes of 16 HAPs in ETS are estimated for US nonsmokers who live with smokers. The evaluation is based on material-balance modeling; utilizes published data on smoking habits, demographics, and housing; and incorporates newly reported exposure-relevant emission factors. The ratio of estimated average exposure concentrations to reference concentrations is close to or greater than one for acrolein, acetaldehyde, 1,3-butadiene, and formaldehyde, indicating potential for concern regarding noncancer health effects from chronic exposures. In addition, lifetime cancer risks from residential ETS exposure are estimated to be substantial ( approximately 2-500 per million) for each of five known or probable human carcinogens: acetaldehyde, formaldehyde, benzene, acrylonitrile, and 1,3-butadiene. Cumulative population intakes from residential ETS are compared for six key compounds against ambient sources of exposure. ETS is found to be a dominant source of environmental inhalation intake for acrylonitrile and 1,3-butadiene. It is an important cause of intake for acetaldehyde, acrolein, and formaldehyde, and a significant contributor to intake for benzene.     

Double exposure. Environmental tobacco smoke

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.     

香烟烟雾对A549与A549-R细胞的氧化损伤

目的探讨hOGG1基因低表达对香烟烟雾作用下细胞氧化损伤效应的影响。方法不同浓度香烟烟雾暴露A549细胞和hOGG1基因低表达的A549-R细胞,MTT实验检测两种细胞存活率,彗星实验观察两种细胞DNA损伤,荧光法测定两种细胞内活性氧(ROS)含量,高效液相色谱-电化学法(HPLC-ECD)检测细胞基因组DNA中8-羟基脱氧鸟苷(8-OHdG)的含量。结果随着香烟烟雾暴露浓度的增加,两种细胞的存活率均下降,且A549-R细胞IC50显著小于A549细胞,差异有统计学意义(P<0.05);两种细胞ROS生成量与香烟烟雾浓度呈剂量-效应关系,当香烟烟雾浓度≥1.25支/升时,A549-R细胞ROS含量显著高于A549细胞(P<0.05);不同香烟烟雾浓度下,A549-R细胞拖尾率、尾长、OTM值均大于A549细胞,差异有统计学意义(P<0.05);A549细胞与A549-R细胞基因组DNA8-OHdG含量随香烟烟雾浓度的增加而升高,当香烟烟雾浓度为2.5支/升和5支/升时,A549-R细胞8-OHdG含量显著高于A549细胞(P<0.05)。结论香烟烟雾可导致A549细胞与A549-R细胞的氧化损伤,hOGG1基因低表达可增加A549-R细胞对香烟烟雾引起的氧化损伤的敏感性。     

香烟侧流烟雾引起的DNA分子氧化损伤

目的：通过研究环境烟草烟雾的侧流烟雾（ETSS）对DNA分子的氧化损伤，探讨环境烟草烟雾（ETS）的遗传毒性效应及其分子机制。方法：以DNA加合物8－羟基脱氧鸟苷（8－OHdG)作为DNA氧化损伤的生物学标志物，用高压液相色谱－电化学检测（HPLC－EC）法对ETSS染毒后的DNA中8－OHdG进行定量检测，通过气质联用法（GC－MS）对香烟烟雾进行有机成分分析和原子吸收法（AAS）对其进行无机元素分析，并从化学组成成分的角度探讨DNA氧化损伤的分子机理。结果：ETSS的颗粒物和挥发性有机物污染物123种和84种，有机元素7种，其中醌类，多酚等化合物具有自氧化作用，不需要任何生物活性系统，在体外就可产生大量的活性氧自由基，并在金属的催化作用下进攻DNA的碱基，形成加合物8－OHdC ,结论：ETSS对DNA具有氧化能力，体现了直接的遗传毒性效应，8－OHdG是DNA氧化损伤较好的效应标志物。     

32P-postlabelling analysis of DNA adducts in monocytes of smokers and passive smokers

Summary In a controlled study, ten male volunteers were subjected to different smoking and passive smoking conditions. After 60 h of strictly controlled nonsmoking, five smokers were exposed to mainstream smoke only, while five nonsmokers were exposed to the gas phase of environmental tobacco smoke (ETS). In a second experiment smokers were mainstream and ETS exposed, while nonsmokers were exposed to complete ETS. Blood was drawn before and after smoking and DNA adducts were analysed from blood monocytes by the³²P-postlabelling assay, using the nuclease P1 enhancement method. We detected DNA adducts in monocytes of all probands. These adducts unrelated to smoking showed interindividual differences but only minor intraindividual changes in four samples of the same donor. After smoking interindividually variable additional adducts were visible in active smokers only. These smoking-related adducts had disappeared after 40 h of nonsmoking and reappeared again in three out of five smokers after the second smoking period. We conclude that smoking causes an interindividually variable pattern of DNA adducts in active smokers. These adducts disappear in less than 2 d, owing to the fast turnover of monocytes in the intravascular system. The effects described could not be observed in heavily exposed passive smokers.     

Maternal smoking during pregnancy and postnatal exposure to environmental tobacco smoke as predisposition factors to acute respiratory infections.

This study compared susceptibility to respiratory morbidity in a cohort of 9-year-old children exposed congenitally and postnatally to environmental tobacco smoke (ETS) to susceptibility in a cohort of unexposed children. The epidemiologic study included 1129 children: 594 boys and 535 girls attending the second grade of grammar schools in Kraków, Poland. We found strong evidence that children exposed to ETS in their homes were more susceptible to acute respiratory tract illnesses than unexposed children. A dose-response relationship between degree of exposure [for lower ETS exposure, odds ratio (OR) = 1.32; for higher ETS exposure, OR = 1.74] supports a causal explanation for the association observed. The significant trend of increased risk of respiratory infections due to ETS level in nonatopic children whose mothers did not smoke cigarettes during pregnancy suggests a direct effect of ETS exposure on the child's respiratory health. ETS combined with allergy nearly tripled the risk of acute respiratory tract illness (OR = 3.39; 95% CI, 1.93-5.93), and maternal smoking during pregnancy had a modifying effect on the risk of respiratory illnesses due to ETS after accounting for atopy. The stronger effect of ETS in atopic children and in those whose mothers smoked during pregnancy may be result of biologic interaction of endogenous and environmental factors. The results of this study are of relevance to public health policy, as children with higher risk of respiratory infections may be more susceptible to environmental hazards later in adolescence or in adulthood. Respiratory infections also increase demands for medical interventions in terms of outpatient services and hospital administrations. In addition, respiratory illnesses cause missed school days, and caring for a sick child may lead to absenteeism from work.     

The tar fraction of cigarette smoke does not promote arteriosclerotic plaque development.

In addition to being the single greatest known environmental cause of cancer, cigarette smoke (CS) is also a major contributor to heart disease. We reported previously that 1) inhalation of either mainstream or sidestream CS promotes aortic arteriosclerotic plaque development; 2) 1,3 butadiene, a vapor-phase component of CS, promotes plaque development at 20 ppm, which at the time was only 2 times higher than the threshold limit value; and 3) individual tar fraction carcinogens in CS, including polynuclear aromatic hydrocarbons (PAHs) and nitrosamines, either do not promote plaque development or do so only at high concentrations. These results suggested that the tar fraction is not the primary source of plaque-promoting agents in CS. We asked whether repeated exposure to the tar fraction of CS, collected in a cold trap (TAR), promotes plaque development in an avian model of arteriosclerosis. Acetone extracts of mainstream CS tar from burning, unfiltered reference cigarettes were solubilized in dimethyl sulfoxide (DMSO) and injected weekly into cockerels for 16 weeks (25 mg/kg/week). Positive controls were injected weekly with the synthetic PAH carcinogen, 7,12 dimethylbenz(a)anthracene (DMBA) dissolved in DMSO and negative controls were injected with DMSO. Plaque location and prevalence did not differ from group to group. Morphometric analysis of plaque cross-sectional areas showed that plaque sizes, which are log-normally distributed, were significantly larger in the DMBA cockerels compared to both the TAR and DMSO groups. There were no significant differences in plaque size between DMSO and TAR cockerels. The results reported here, combined with other recent findings, support the conclusion that the primary arteriosclerotic plaque-promoting components of CS are in the vapor phase.     

The smoke you don't see: uncovering tobacco industry scientific strategies aimed against environmental tobacco smoke policies

OBJECTIVES: This review details the tobacco industry's scientific campaign aimed against policies addressing environmental tobacco smoke (ETS) and efforts to undermine US regulatory agencies from approximately 1988 to 1993. METHODS: The public availability of more than 40 million internal, once-secret tobacco company documents allowed an unedited and historical look at tobacco industry strategies. RESULTS: The analysis showed that the tobacco industry went to great lengths to battle the ETS issue worldwide by camouflaging its involvement and creating an impression of legitimate, unbiased scientific research. CONCLUSIONS: There is a need for further international monitoring of industry-produced science and for significant improvements in tobacco document accessibility.     

Respiratory health consequences of environmental tobacco smoke

Over the last several decades there has been a growing interest in examining the health consequences of environmental tobacco smoke (ETS). As a result of a wide body of research, ETS is now considered an unacceptable and entirely preventable public health hazard, and public policy increasingly discourages the presence of tobacco smoke in the public domain. This article provides an overview of the composition of ETS and the major diseases and disorders strongly linked to ETS, emphasizing the effects of ETS on pulmonary function, asthma, and lung cancer.     

Disease burdens from environmental tobacco smoke in Korean adults

In this study, we estimated the disease burdens attributable to environmental tobacco smoke (ETS) exposure in Korean adults in 2010 and analyzed the trend of that from 2005 to 2010. We obtained information on the study population from the 2010 Cause of Death Statistic and estimated the ETS-attributable fraction using data from the Korean Community Health Survey and the Korean National Health and Nutrition Examination Survey. The numbers of ETS-attributable deaths in female and male non-smokers were estimated to be 4.1 and 69.6?% of the numbers of deaths attributable to current smoke, respectively. The deaths attributable to ETS were larger in female than in male non-smokers (710 vs. 420). The ETS-attributable deaths increased slightly in 2005–2008 but decreased in 2009–2010. The number of potential years of life lost from ETS was 9077.24?years in 2010. If there were no exposure to ETS in adult non-smokers, we would expect to see 1130 fewer deaths (9.9?% of the deaths from current smoke). The results suggest that ETS poses considerable disease burdens for non-smokers, especially women, in Korea.     

Association of prenatal maternal or postnatal child environmental tobacco smoke exposure and neurodevelopmental and behavioral problems in children

We review the potential neurodevelopmental and behavioral effects of children's prenatal and/or postnatal exposure to environmental tobacco smoke (ETS). Children's exposure to ETS has been assessed in epidemiologic studies as a risk factor for a variety of behavioral and neurodevelopmental problems including reduced general intellectual ability, skills in language and auditory tasks, and academic achievement, and behavioral problems such as hyperactivity and decreased attention spans. We review 17 epidemiologic studies that have attempted to separate the effects of maternal active smoking during pregnancy from passive ETS smoke exposure by the pregnant mother or the child. Based on the available data, we found that ETS exposure could cause subtle changes in children's neurodevelopment and behavior. However, studies to date are difficult to interpret because of the unknown influence of uncontrolled confounding factors, imprecision in measurements of smoking exposure, and collinearity of pre- and postnatal maternal smoking. Although some evidence suggests that maternal smoking during pregnancy may be associated with deficits in intellectual ability and behavioral problems in children, the impact of prenatal or postnatal ETS exposure remains less clear.     

Lifetime environmental tobacco smoke exposure and the risk of chronic obstructive pulmonary disease

Background  

Exposure to environmental tobacco smoke (ETS), which contains potent respiratory irritants, may lead to chronic airway inflammation and obstruction. Although ETS exposure appears to cause asthma in children and adults, its role in causing COPD has received limited attention in epidemiologic studies.