Agents In Tobacco Smoke Research Articles

Cooking up low-acrylamide foods

The Maillard reaction is arguably the world’s most beloved chemical process. Cooks learned long ago that raw, unappetizing ingredients such as potatoes and grains can be turned into toasty treats with the addition of heat and a bit of time. Chemists know our enjoyment is due to the magic that happens when amino acids meet sugars to produce mouthwatering organic compounds such as pyrazines, pyrroles, and furanones. But in 2002 the food world learned that this browning reaction has a dark side. It turns out that one of those Maillard products is acrylamide, a chemical long known to cause cancer in animal studies. In humans, it is considered likely to be carcinogenic and has been identified as a cancer-causing agent in tobacco smoke. Acrylamide is used industrially to make polyacrylamides–water-soluble thickeners widely used in grouts and water treatment facilities. Because of acrylamide’s human health effects, regulators including the US Environmental

Critical developmental periods for effects of low-level tobacco smoke exposure on behavioral performance

Tobacco exposure during development leads to neurobehavioral dysfunction in children, even when exposure is limited to secondhand smoke. We have previously shown in rats that developmental exposure to tobacco smoke extract (TSE), at levels mimicking secondhand smoke, starting preconception and extending throughout gestation, evoked subsequent locomotor hyperactivity and cognitive impairment. These effects were greater than those caused by equivalent exposures to nicotine alone, implying that other agents in tobacco smoke contributed to the adverse behavioral effects. In the present study, we examined the critical developmental windows of vulnerability for these effects, restricting TSE administration (0.2 mg/kg/day nicotine equivalent, or DMSO vehicle, delivered by subcutaneously-implanted pumps) to three distinct 10 day periods: the 10 days preceding mating, the first 10 days of gestation (early gestation), or the second 10 days of gestation (late gestation). The principal behavioral effects revealed a critical developmental window of vulnerability, as well as sex selectivity. Late gestational TSE exposure significantly increased errors in the initial training on the radial-arm maze in female offspring, whereas no effects were seen in males exposed during late gestation, or with either sex in the other exposure windows. In attentional testing with the visual signal detection test, male offspring exposed to TSE during early or late gestation showed hypervigilance during low-motivating conditions. These results demonstrate that gestational TSE exposure causes persistent behavioral effects that are dependent on the developmental window in which exposure occurs. The fact that effects were seen at TSE levels modeling secondhand smoke, emphasizes the need for decreasing involuntary tobacco smoke exposure, particularly during pregnancy.

Association of CYP2A6 activity with lung cancer incidence in smokers: The multiethnic cohort study.

While smoking is the primary cause of lung cancer, only 11–24% of smokers develop the malignancy over their lifetime. The primary addictive agent in tobacco smoke is nicotine and variation in nicotine metabolism may influence the smoking levels of an individual. Therefore, inter-individual variation in lung cancer risk among smokers may be due in part to differences in the activity of enzymes involved in nicotine metabolism. In most smokers, cytochrome P450 2A6 (CYP2A6)-catalyzed C-oxidation accounts for >75% of nicotine metabolism, and the activity of this enzyme has been shown to correlate with the amount of nicotine and carcinogens drawn from cigarettes. We prospectively evaluated the association of urinary biomarkers of nicotine uptake (total nicotine equivalents [TNE]) and CYP2A6 activity (ratio of urinary total trans-3′-hydroxycotinine to cotinine) with lung cancer risk among 2,309 Multiethnic Cohort Study participants who were current smokers at time of urine collection; 92 cases were diagnosed during a mean follow-up of 9.5 years. We found that higher CYP2A6 activity and TNE was associated with increased lung cancer risk after adjusting for age, sex, race/ethnicity, body mass index, smoking duration, and urinary creatinine (p’s = 0.002). The association for CYP2A6 activity remained even after adjusting for self-reported cigarettes per day (CPD) (Hazard Ratio [HR] per unit increase in log-CYP2A6 activity = 1.52; p = 0.005) and after adjusting for TNE (HR = 1.46; p = 0.01). In contrast, the association between TNE and lung cancer risk was of borderline statistical significance when adjusted for CPD (HR = 1.53; p = 0.06) and not statistically significant when further adjusted for CYP2A6 activity (HR = 1.30; p = 0.22). These findings suggest that CYP2A6 activity provides information on lung cancer risk that is not captured by smoking history or a (short-term) biomarker of dose. CYP2A6 activity should be further studied as a risk biomarker for smoking-related lung cancer.

European Code against Cancer, 4th Edition: Tobacco and cancer

Tobacco use, and in particular cigarette smoking, is the single largest preventable cause of cancer in the European Union (EU). All tobacco products contain a wide range of carcinogens. The main cancer-causing agents in tobacco smoke are polycyclic aromatic hydrocarbons, tobacco-specific N-nitrosamines, aromatic amines, aldehydes, and certain volatile organic compounds. Tobacco consumers are also exposed to nicotine, leading to tobacco addiction in many users. Cigarette smoking causes cancer in multiple organs and is the main cause of lung cancer, responsible for approximately 82% of cases. In 2012, about 313,000 new cases of lung cancer and 268,000 lung cancer deaths were reported in the EU; 28% of adults in the EU smoked tobacco, and the overall prevalence of current use of smokeless tobacco products was almost 2%. Smokeless tobacco products, a heterogeneous category, are also carcinogenic but cause a lower burden of cancer deaths than tobacco smoking. One low-nitrosamine product, snus, is associated with much lower cancer risk than other smokeless tobacco products. Smoking generates second-hand smoke (SHS), an established cause of lung cancer, and inhalation of SHS by non-smokers is still common in indoor workplaces as well as indoor public places, and more so in the homes of smokers. Several interventions have proved effective for stopping smoking; the most effective intervention is the use of a combination of pharmacotherapy and behavioural support. Scientific evidence leads to the following two recommendations for individual action on tobacco in the 4th edition of the European Code Against Cancer: (1) “Do not smoke. Do not use any form of tobacco”; (2) “Make your home smoke-free. Support smoke-free policies in your workplace”.

Abstract 2721: Induction of aberrant crypt foci in the colon of mice exposed to tobacco carcinogen 2-amino-9H-pyrido[2,3-b]indole

Abstract Epidemiological studies indicate that tobacco smoking is a risk factor for colon cancer. However, the etiological agents in tobacco smoke remain uncertain. Heterocyclic aromatic amines (HAAs) that are produced during high-temperature cooking of the proteinaceous food are associated with the elevated risk of colon cancer. Tobacco smoking also produces HAAs, the most abundant one being 2-amino-9H-pyrido[2,3-b]indole (AαC). The carcinogenic potency of AαC is unknown in humans, but AαC forms DNA adducts in multiple organs, including liver and colon, as well as being carcinogenic in rodents. In this study, AαC-induced colon cancer risk was assessed by determining DNA adducts and putative colonic precancerous lesions, aberrant crypt foci (ACF) and dysplastic ACF. For comparison, the HAA, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a liver and colon carcinogen in mice, and azoxymethane (AOM), a potent colon carcinogen in rodents, were also administered. AαC (400 ppm) or MeIQ (300 ppm) were fed in a high-fat diet to A/J mice (n = 12 per group) for 4 weeks. AOM was injected intraperitoneally to another 12 mice at 5 mg/kg body weight weekly for 6 weeks. At the end of carcinogen treatment, liver and colon were harvested from 4 mice from each group for DNA adduct measurement. dG-C8-AαC, dG-C8-MeIQ, and O6-methyl-dG DNA adducts were measured by liquid chromatography/mass spectrometry. The remaining 8 mice from each group were then fed a carcinogen-free diet for additional 8 weeks, and then colons harvested. Colonic total and dysplastic ACF were counted by light microscopy after appropriate staining. AαC feeding induced the greatest number of DNA adducts in liver, followed by AOM and MeIQ. AOM administration and AαC feeding induced similar numbers of DNA adducts in the colon, both of which were significantly greater than MeIQ. However, AOM administration induced a significantly greater number of total and dysplastic ACF in the colons than did feeding either AαC or MeIQ, which had similar numbers of ACF and dysplastic ACF. The high levels of AαC DNA adducts and induced dysplastic ACF in this animal model, provide biological plausibility for a causal role for AαC in tobacco-induced colorectal carcinogenesis. However, DNA adduct numbers induced by these three carcinogens was not proportional to the colonic ACF or dysplastic ACF number, suggesting that different types of DNA adducts differ in their ability to promote colonic precancerous lesions. Citation Format: Sangyub Kim, Jingshu Guo, Sabrina P. Trudo, Daniel D. Gallaher, Robert J. Turesky. Induction of aberrant crypt foci in the colon of mice exposed to tobacco carcinogen 2-amino-9H-pyrido[2,3-b]indole. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2721. doi:10.1158/1538-7445.AM2015-2721

Orally administered nicotine induces urothelial hyperplasia in rats and mice

Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52ppm nicotine) and mice (514ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a mitogenic effect of nicotine and/or its metabolites.

An Omics Strategy for Discovering Pulmonary Biomarkers Potentially Relevant to the Evaluation Of Tobacco products

Smoking is known to cause serious lung diseases including chronic bronchitis, chronic obstructive lung disease, obstruction of small airways, emphysema and cancer. Tobacco smoke is a complex chemical aerosol containing at least 8000 chemical constituents, either tobacco derived or added by tobacco product manufacturers. Identification of all of the toxic agents in tobacco smoke is challenging, and efforts to understand the mechanisms by which tobacco use causes disease will be informed by new biomarkers of exposure and harm. In 2009, President Obama signed into law the Family Smoking Prevention and Tobacco Control Act granting the US FDA the authority to regulate tobacco products to protect public health. This perspective article presents the background, rationale and strategy for using omics technologies to develop new biomarkers, which may be of interest to the FDA when implementing the Family Smoking Prevention and Tobacco Control Act.

Development of novel pharmacotherapeutics for tobacco dependence: progress and future directions.

The vast majority of tobacco smokers seeking to quit will relapse within the first month of abstinence. Currently available smoking cessation agents have limited utility in increasing rates of smoking cessation and in some cases there are notable safety concerns related to their use. Hence, there is a pressing need to develop safer and more efficacious smoking cessation medications. Here, we provide an overview of current efforts to develop new pharmacotherapeutic agents to facilitate smoking cessation, identified from ongoing clinical trials and published reports. Nicotine is considered the major addictive agent in tobacco smoke, and the vast majority of currently available smoking cessation agents act by modulating nicotinic acetylcholine receptor (nAChR) signaling. Accordingly, there is much effort directed toward developing novel small molecule therapeutics and biological agents such as nicotine vaccines for smoking cessation that act by modulating nAChR activity. Our increasing knowledge of the neurobiology of nicotine addiction has revealed new targets for novel smoking cessation therapeutics. Indeed, we highlight many examples of novel small molecule drug development around non-nAChR targets. Finally, there is a growing appreciation that medications already approved for other disease indications could show promise as smoking cessation agents, and we consider examples of such repurposing efforts. Ongoing clinical assessment of potential smoking cessation agents offers the promise of new effective medications. Nevertheless, much of our current knowledge of molecular mechanisms of nicotine addiction derived from preclinical studies has not yet been leveraged for medications development.

The Delivery of Stop Smoking Support to People with Mental Health Conditions: A Survey of NHS Stop Smoking Services

BackgroundPeople with mental health problems exhibit smoking rates up to three times that of the general population. Metabolic interactions between hydrocarbon agents in tobacco smoke and some antipsychotic drugs account for a change in medication metabolism on stopping smoking, and potentially for increased blood levels. Nicotine withdrawal can mimic or exacerbate symptoms of mental illness. Therefore, appropriate screening for mental health problems and liaison with local mental health care providers should be a priority for NHS Stop Smoking Services. The present study aimed to examine this issue through surveys with NHS Stop Smoking Service staff in London.MethodsSemi-structured telephone interviews were conducted with one senior staff member from 27 of the 29 NHS Stop Smoking Services in London.ResultsIt was found that only a minority of services routinely check the mental health status or mental health service use of their clients. In addition, most services do not routinely implement special checks or actions when mental health problems are revealed. It was notable that respondents reported a lack of strategic drivers supporting work with mental health patients (such as targets relating to successful quits) as well as a low level of partnership working with local mental health care providers.ConclusionsNHS Stop Smoking Services may not be operating appropriate procedures for supporting people with mental health problems. There is a need for local protocols to be implemented that include routine screening for mental health issues and liaison with mental health care providers.

Nicotine exposure throughout early development promotes nicotine self-administration in adolescent mice and induces long-lasting behavioural changes

Maternal cigarette smoking during pregnancy can result in behavioural problems of the offspring. Although the causative agent in tobacco smoke that leads to these aberrations is not known, some studies using animal models have supported the hypothesis that nicotine may cause impairments in fatal and neonatal development. However, in many of the animal studies nicotine has been administered by subcutaneous injections, which could lead to significant fetal hypoxia; some routes of drug administration included stressful procedures to pregnant dams that could create unfavorable fetal environment. In this study, mice were exposed to nicotine via drinking solution. The effects of nicotine exposure throughout early development on behavioural measures during adolescence and adulthood were examined. Adult female dams were allowed to orally self-administer a saccharin, or nicotine plus saccharin solution during gestation and lactation. Following weaning, plasma nicotine concentrations were measured in nicotine-exposed dams, and their offspring were tested using various behavioural measures. [ 3H]Epibatidine binding was also measured in the cortex and hippocampus at two different time points in the nicotine-exposed adolescents. The results of the study indicate that exposure to nicotine throughout early development influenced intravenous nicotine self-administration, social interactions and performance under a forced swim test. Exposure throughout early development to nicotine however did not affect [ 3H]epibatidine binding in the hippocampus and cortex.

Nicotine Metabolism in African Americans and European Americans: Variation in Glucuronidation by Ethnicity and UGT2B10 Haplotype

Nicotine is the major addictive agent in tobacco smoke, and it is metabolized extensively by oxidation and glucuronide conjugation. The contributions of ethnicity and UGT2B10 haplotype on variation in nicotine metabolism were investigated. Nicotine metabolism was evaluated in two populations of smokers. In one population of African American and European American smokers (n = 93), nicotine and its metabolites were analyzed in plasma and 24-h urine over 3 days while participants were abstinent and at steady state on the nicotine patch. In a second study of smokers (n = 84), the relationship of a UGT2B10 haplotype linked with D67Y to nicotine and cotinine glucuronidation levels was determined. We observed that both African American ethnicity and the UGT2B10 D67Y allele were associated with a low glucuronidation phenotype. African Americans excreted less nicotine and cotinine as their glucuronide conjugates compared with European Americans; percentage of nicotine glucuronidation, 18.1 versus 29.3 (p < 0.002) and percentage of cotinine glucuronidation, 41.4 versus 61.7 (p < 0.0001). In smokers with a UGT2B10 Tyr67 allele, glucuronide conjugation of nicotine and cotinine was decreased by 20% compared with smokers without this allele. Two key outcomes are reported here. First, the observation that African Americans have lower nicotine and cotinine glucuronidation was confirmed in a population of abstinent smokers on the nicotine patch. Second, we provide the first convincing evidence that UGT2B10 is a key catalyst of these glucuronidation pathways in vivo.

In utero nicotine exposure causes persistent, gender-dependant changes in locomotor activity and sensitivity to nicotine in C57Bl/6 mice

Maternal cigarette smoking during pregnancy can result in a wide variety of adverse fetal outcomes, ranging from preterm delivery and low birth weight, to sudden infant death syndrome. In addition, in utero tobacco smoke exposure is associated with delayed or impaired neuropsychological development. Although the causative agent in tobacco smoke that leads to these aberrations is not known, some studies have concluded that nicotine may play an important role. Many studies using animal models of prenatal nicotine exposure have supported the hypothesis that nicotine may directly and/or indirectly cause impairments in fetal and neonatal development. However, in many of the animal studies nicotine has been administered acutely to naive dams, which could lead to significant fetal hypoxia; some routes of drug administration are also very stressful to pregnant dams, and changes in stress hormones could also create an unfavorable fetal environment. In this study, pregnant mice were exposed to chronic nicotine via the drinking solution; locomotor activity and sensitivity to nicotine were evaluated in the offspring. We have previously shown that oral nicotine administration produces behavioral and physiological changes that resemble those seen following other routes of nicotine administration. Although oral nicotine exposure did not significantly alter any aspect of the pregnancy, dams drinking a nicotine-containing solution consumed approximately 20% less volume, compared to saccharin controls. All animals were cross fostered to nicotine naı̈ve lactating dams, immediately after birth. On PN40 and PN60, male mice exposed to in utero nicotine demonstrated significant locomotor hyperactivity in an open filed arena. Although female animals did not show any signs of hyperactivity, they did have a significant attenuation of their hypothermic response to acute nicotine challenge. These results suggest that oral nicotine delivery to pregnant mice causes persistent, gender-dependant changes in behavior and sensitivity to nicotine. This model may be very useful for future studies that try to more accurately define the windows of sensitivity for nicotine exposure and the possible underlying neurochemical mechanisms involved.

O-80 Carcinogenic agents in tobacco smoke: information from the cigarette packs

O-80 Carcinogenic agents in tobacco smoke: information from the cigarette packs

Detection of human exposure to carcinogens by measurement of alkyl-DNA adducts using immunoaffinity clean-up in combination with gas chromatography-mass spectrometry and other methods of quantitation

A brief overview is given of recent developments from our laboratory in the use of immunoaffinity clean-up in the determination of alkyl-DNA adducts. Compound- and group-specific antibodies have been prepared against 7-alkylguanines and 3-alkyladenines. The antibodies were attached to solid supports to make immunoaffinity columns which could then be used to selectively purify either single adducts or groups of adducts prior to quantitation by various methods. In the case of methyl adducts quantitation was achieved by ELISA (3-methyl-adenine, using a monoclonal antibody) and HPLC-electrochemical detection (7-methylguanine). For groups of adducts, quantitation of the individual compounds was effected by gas chromatography-mass spectrometry (3-alkyladenines, using deuterated analogues of each adduct as an internal standard) and HPLCL-fluorescence detection (7-alkylguanines). In all of these cases efficient purification of adducts from urine or DNA hydrolysates could be easily carried out. Using these techniques human exposure to alkylating agents in tobacco smoke and from cancer chemotherapy has been studied.

Occupation and chronic obstructive pulmonary disease (COPD)

Chronic bronchitis, defined as increased cough and sputum production, is well established as an occupational disease independent of cigarette smoking, which is a major confounding factor. The relevance of industrial exposure to the development of airflow obstruction (chronic obstructive pulmonary disease (COPD)) is more controversial. Good data exist linking the inhalation of cadmium fume to the development of emphysema. The pathology of airflow obstruction due to other occupational exposures is less clear. The principal measure of occupational bronchitis with airflow obstruction is accelerated loss of forced expiratory volume in one second (FEV1); and epidemiology is the principal tool for investigation. Using these methods, many workers have established links between occupational exposure and disease, which will be reviewed. From an occupational standpoint tobacco smoking is unique, in that the pollutant is put into the mouth and deliberately inhaled in concentrations far exceeding occupational exposures. Despite this, less than 20% of smokers develop significant airflow obstruction. The factors which determine whether an individual smoker develops airflow obstruction are usually unknown. There are two ways in which an occupational agent may act: 1) by promoting the deleterious effects of smoking; or 2) by acting in a manner similar to tobacco smoking, requiring other promoting factors before an effect is seen. Examples will be given of both of these mechanisms. From a pragmatic point of view, it is highly unlikely that the mixed agents in tobacco smoke are the only cause of significant COPD. The widespread habit of tobacco smoking in industrial populations has delayed the recognition of other factors contributing to disease, as it is only possible to examine the independent risks of smoking and occupational exposures when a reasonable proportion of those occupationally exposed are lifelong nonsmokers. The studies of specific workforces are often difficult to interpret, as workers commencing exposure in jobs with a high risk of lung disease have even better lung function than the normal worker, and losses from a cohort are higher in those with disease, leading to lower estimates of risk as an increasingly smaller proportion of survivors are followed-up. These problems have been overcome by sampling the general population away from the workplace. Such studies suffer from less selection bias (but exclude those who have died prematurely), and have less satisfactory estimates of occupational exposure, usually including a greater proportion of those with low exposure and, thus, reducing the relative risks of exposure. Such studies have included a general older working population in Beijing (China) [1], an urban and rural population in Norway [2], a rural population in Northern Italy [3], and two studies of city dwellers designed to investigate air pollution in France [4] and the USA [5]. Different outcome measures have been used, but all show significant excess risks with occupation. In general, dust exposure is associated with higher risks of reduced lung function than gas or fume exposure [1, 5], with relative risks of around 1.5. General population samples have been studied longitudinally in Paris [6], Cracow (Poland) [7], Zutphen (Holland) [8] and Bergen (Norway) [9]. The Zutphen study again started with a community sample, using a job matrix to link symptoms and diagnoses with the occupation. The study has been analyzed longitudinally, initially using the time, intensity and duration of exposure. The longitudinal analysis found a cumulative 25 yr incidence of chronic nonspecific lung disease of 27.9%. Incidence density ratios were calculated, and ratios for smoking increased from 1.5 for light smokers to 4.5 for those smoking more than 20 cigarettes daily. Increased risks of chronic nonspecific lung disease (which includes asthma), were found in a number of occupations which are shown in table 1. A further analysis of this study, by the same group, appears in this issue of the Journal [10], using a different job exposure matrix generated from the sample itself. It is disappointing that the results of the reanalysis are less clear than the original analysis, perhaps because of the lack of differentiation between the proportion of the workforce exposed to a particular agent, and its intensity. The mortality analysis was limited by the small number of deaths (33 out of 799) due to chronic nonspecific lung disease. Nevertheless, for occupational groups where at

Relationship Between K-ras Oncogene Activation and Smoking in Adenocarcinoma of the Human Lung

To investigate a possible relationship between the exposure to tobacco smoke and the presence of ras point mutations, we examined lung adenocarcinoma samples from 27 smokers and from 27 nonsmokers. Activating point mutations in K-ras (also known as KRAS2) and N-ras (also known as NRAS) were determined by using the polymerase chain reaction and oligonucleotide hybridization to detect the mutated sequences. Mutations were more often found in adenocarcinomas obtained from smokers (eight of 27) than in adenocarcinomas obtained from nonsmokers (two of 27) (P = .044, Fisher's exact test). All mutations were present in K-ras codon 12. None of the other parameters examined differed significantly between the ras-positive and ras-negative groups. We conclude that exposure to carcinogenic agents in tobacco smoke is an important factor in the induction of point mutations in K-ras in human lung adenocarcinomas, but that K-ras mutations may also infrequently occur in tumors of non-smokers.

Smoking and Hormone-Related Disorders

RESULTS FROM THREE PROSPECTIVE STUDIES: Smoking and oestrogen-related sites - data from American cancer studies Smoking and hormone-related disorders in the Nurses' Health Study Effects of cigarette smoking on 'hormone-related' diseases in a Southern Californian retirement community SMOKING, THE MENOPAUSE, AND THE BENIGN REPRODUCTIVE DISORDERS: Cigarette smoking and age at natural menopause Hyperemesis gravidarum, uterine fibroids, and endometriosis: effects of cigarette smoking on risk Cigarette smoking and benign breast cancer SMOKING AND OSTEOPOROSIS: Smoking and osteoporosis Cigarette smoking and skin atrophy in women - a possible connection? Smoking and prostatic hypertrophy Smoking and inflammatory bowel disease Smoking and PArkinson's disease SMOKING AND HORMONE-RELATED CANCERS: Cigarette smoking and the incidence of endometrial cancer Cigarette smoking and cancer of the breast Cigarette smoking and cancer of the large bowel MECHANISMS: HORMONAL DIFFERENCES IN SMOKERS AND NON-SMOKERS: Smoking and endogenous sex hormones in men and women Increased oxidative metabolism of oestrogens in male and female smokers The effect of smoking on hormone levels in vivo and steroid hormone biosynthesis in vitro. MECHANISMS: HORMONES OF POSSIBLE RELEVANCE TO SMOKING-RELATED DISEASES: Oestrogens and smoking-related disease: theoretical considerations Hormonal factors and cancers of the endometrium and breast MECHANISMS: THE ROLE OF NICOTINE AND OTHER AGENTS IN TOBACCO SMOKE: Influence of nicotine and other components of tobacco smoke on oestradiol metabolism Oestrogen 2-hydroxylation in rat and human liver SUMMARY AND IMPLICATIONS: Smoking and hormone-related disorders: a summary of the evidence with implications for public health policy and future research.

Indoor Dust Exposure: An Unnoticed Aspect of Involuntary Smoking

The nicotine concentration in samples of house dust from the homes of 34 smokers and 38 nonsmokers was analyzed using a gas chromatographic method. A strong positive correlation (r = .65, p less than .0001) between the amount smoked and the nicotine concentration in the house dust was found when the results from all homes were analyzed, and a fairly strong positive correlation (r = .35, p less than .05) was found for smokers' homes only. These data suggest that the nonsmoker may inhale tobacco constituents from respirable dust, even if smoking does not occur. The amount of nicotine inhaled during 1 h was estimated for someone in one of the homes where there was a high nicotine concentration in the house dust. The calculated amount, 12 ng, is very small compared with the amount inhaled when active smoking occurs (i.e., 600-3,000 ng/h). In this study, nicotine was a marker of tobacco pollution. Assuming that other tobacco smoke agents have a similar or smaller affinity to house dust as that of nicotine, we conclude that house dust inhalation constitutes only a modest additional source of involuntary smoking.

Some long term effects of smoking on the haemostatic system: a report from the Caerphilly and Speedwell Collaborative Surveys.

Data from two community studies on men from South Wales and the west of England suggest that the effects of smoking on the haemostatic system remain for many years after giving up. Long term correlations between several variables, including plasma fibrinogen and white cell count, and the length of time after giving up were seen in ex-smokers. Dose response relations were apparent in current smokers in terms of the white cell count and two haematological variables, the packed and mean cell volumes. These long term correlations probably reflect the toxicity of other agents in tobacco smoke besides nicotine and carbon monoxide, which act only in the short term. Identification of these agents may further our understanding of the mechanism by which cigarette smoking is associated with atherosclerotic disease.

The effect of intermittent carbon monoxide exposure on experimental atherosclerosis in the rabbit

1. (1) Twenty-four female New Zealand White rabbits were fed commercial diet plus 2% cholesterol. Twelve of these animals were exposed to carbon monoxide for 4 hours per day, seven days per week for 10 weeks. The carbon monoxide exposure was such that the mean blood carboxy-haemoglobin was raised to approximately 20% during each exposure period. Twelve control animals breathed atmospheric air under the same conditions of confinement as the carbon monoxide-exposed group. 2. (2) No significant differences in the plasma levels of cholesterol, triglycerides or glutamate oxalacetate transaminase were observed between the two groups during the experiment. 3. (3) When the animals were sacrificed at the end of the experiment no significant differences were observed between the two groups in the aortic content of triglycerides, cholesterol or phospholipids. 4. (4) The extent of coronary artery atherosclerosis was statistically significantly higher in the carbon monoxide group than in the control group. 5. (5) Ultracentrifugal analysis of plasma lipoproteins revealed that there was significantly more cholesterol in the d < 1.006 fraction from the CO-exposed rabbits. 6. (6) These findings, are discussed with particular reference to the claim that the causal agent in tobacco smoke associated arterial disease is carbon monoxide.