Chronic Cigarette Smoke Inhalation Research Articles

Testicular tissue response following a 90-day subchronic exposure to HTP aerosols and cigarette smoke in rats.

Researches have shown that chronic inhalation of cigarette smoke (CS) disrupts male reproductive system, but it is unclear about the mechanisms behind reproductive damages by tobacco toxicants in male rats. This study was designed to explore the effects of heated tobacco products (HTP) aerosols and CS exposure on the testicular health of rats. Experiments were performed on male SD rats exposed to filtered air, HTP aerosols at 10 μg/L, 23 μg/L, and 50 μg/L nicotine-equivalent contents, and also CS at 23 μg/L nicotine-equivalent content for 90 days in five exposure groups (coded as sham, HTP_10, HTP_23, HTP_50 and Cig_23). The expression of serum testosterone, testicular tissue inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α), reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA), NLRP3 inflammasome-related mRNAs and proteins (NLRP3, ASC, and Caspase-1), the degree of pyroptosis and histopathology were investigated. The results demonstrated that HTP_50 and Cig_23 caused varying degrees of oxidative damage to rat testis, resulting in a decrease of sperm quantity and serum testosterone contents, an increase in the deformity rate, expression levels of proinflammatory cytokines, and NLRP3 inflammasome-related mRNA, and an increase in the NLRP3, ASC, and Caspase-1-immunopositive cells, pyroptosis cell indices, and histopathological damage in the testes of rats. Responses from the HTP_10 and HTP_23 groups were less than those found in the above two exposure groups. These findings indicate that HTP_50 and Cig_23 induced oxidative stress in rat testes, induced inflammation and pyroptosis through the ROS/NLRP3/Caspase-1 pathway, and destroyed the integrity of thetesticular tissue structure.

Role of oxidative stress in the pathogenesis of COPD.

Chronic inhalation of cigarette smoke is a prominent cause of chronic obstructive pulmonary disease (COPD) and provides an important source of exogenous oxidants. In addition, several inflammatory and structural cells are a source of endogenous oxidants in the lower airways of COPD patients, even in former smokers. This suggests that oxidants play a key role in the pathogenesis of COPD. This oxidative stress is counterbalanced by the protective effects of the various endogenous antioxidant defenses of the lower airways. A large amount of data from animal models and patients with COPD have shown that both the stable phase of the disease, and during exacerbations, have increased oxidative stress in the lower airways compared with age-matched smokers with normal lung function. Thus, counteracting the increased oxidative stress may produce clinical benefits in COPD patients. Smoking cessation is currently the most effective treatment of COPD patients and reduces oxidative stress in the lower airways. In addition, many drugs used to treat COPD have some antioxidant effects, however, it is still unclear if their clinical efficacy is related to pharmacological modulation of the oxidant/antioxidant balance. Several new antioxidant compounds are in development for the treatment of COPD.

The role of airway remodeling in the pathogenesis and treatment of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is currently considered the third leading cause of death in the world. COPD represents an important public health challenge and a socio-economical problem that is preventable and treatable. The main cause of COPD is chronic inhalation of cigarette smoke, and other harmful constituents of air pollution, which cause epithelial injury, chronic inflammation and airway remodeling. Airway remodeling is most prominent in small airways. It is due to infiltration of the airways by inflammatory cells, such as neutrophils, eosinophils, macrophages, and immune cells, including CD8+ T-cells, Th1, Th17 lymphocytes, and innate lymphoid cells group 3. Fibroblasts, myofibroblasts, and airway smooth muscle (ASM) cells also contribute to airway remodeling by depositing extracellular matrix (ECM) proteins, which increase the thickness of the airway wall. Activated inflammatory cells, and structural cells secrete cytokines, chemokines, growth factors, and enzymes which propagate airway remodeling. Airway remodeling is an active process which leads to thickness of the reticular basement membrane, subepithelial fibrosis, peribronchiolar fibrosis, and ASM cells hyperplasia and hypertrophy. It is also accompanied by submucosal glands and goblet cells hypertrophy and mucus hypersecretion, and angiogenesis. Epithelial mesenchymal transmission (EMT) plays a key role in airway remodeling. In patients with COPD and smokers, cellular reprograming in epithelial cells leads to EMT, whereby epithelial cells assume a mesencymal phenotype. Additionally, COPD is associated with increased parasympathetic cholinergic activity, which leads to ASM cells hypercontractility, increased mucus secretion, and vasodilatation. Treatment of COPD is intricate because of the heterogeneous nature of the disease, which requires specific treatment of the pathophysiological pathways, such as airway inflammation, ASM cell hypercontractility, and parasympathetic cholinergic hyperreactivity. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 strategy report recommends personalized approach for the treatment of COPD. However, some patients with COPD are unresponsive to the standards of care. They may require a triple combination of LABA/LAMA/ICS. Single-inhaler triple therapy (SITT), such as fluticasone fuorate/vilanterol/umeclidinium has been shown to significantly improve symptoms and asthma control, reduce moderate and severe exacerbations, and to improve lung function.

The Effects of Passive Smoking on Laryngeal and Tracheal Mucosa in Male Wistar Rats During Growth: An Experimental Study

Cigarettes contain toxic and carcinogenic substances. In this context, cigarette smoking, and similar activities, are associated with numerous pathologies, being considered a risk factor in up to 10% of the total number of deaths in adults. Recent evidence suggests that the exposure of children to smoking in the early days of their development causes many diseases. Using light microscopy, this study aims to analyze the possible histopathological effects of an experimental model of chronic inhalation of cigarette smoke (passive smoking) on the laryngeal and tracheal mucosa of young Wistar rats. A total of 24 young Wistar rats were studied for a period of 120 days. The animals were divided into two groups: passive smoking (n = 16) and control (n = 8). The level of exposure to cigarette smoke was evaluated from the urinary cotinine level. Although no cancerous lesions were identified, histopathological analysis in the laryngeal and tracheal mucosa of all the animals in the experimental group showed that the proportion of moderate and focal inflammation was higher in animals exposed to chronic inhalation of cigarette smoke (P = 0.041). Histopathologic analysis revealed moderate and focal inflammatory lesions in the region of the infraglottic mucosa in exposed animals, although without dysplastic or neoplastic lesions in the laryngeal and tracheal mucosa.

Chronic inhalation of cigarette smoke reduces phagocytosis in peripheral blood leukocytes.

BackgroundPhagocytosis activity of peripheral blood leukocytes in smokers or chronic obstructive pulmonary disease patients was found to be controversial and dependent on the phagocytic stimulus.ResultsWe demonstrated that long-term exposure to cigarette smoke in mice clearly suppressed the phagocytosis of granulocytes and monocytes from peripheral blood.ConclusionsImpaired phagocytosis activity of peripheral blood leukocytes may have a systemic effect and potentially contribute to smoking-associated diseases such as pneumonia and lung cancer.

Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema.

Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c(+) lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.

The effect of smoking on expression of IL-6 and antioxidants in pancreatic fluids and tissues in patients with chronic pancreatitis

ObjectivesThe present study was conducted to ascertain whether cigarette smoke induces oxidative stress in the human pancreas concurrently with inflammation. Materials and methodsThe influence of tobacco smoking on the serum level of interleukin-6 (IL-6), on the activities of glutathione peroxidase (GPx) and copper–zinc superoxide dismutase (Cu/Zn SOD) as well as on the metallothionein (MT) level in the pancreatic pseudocyst fluid and its immunohistochemical localization in tissues of non-smoking (n = 9) and smoking (n = 12) patients with diagnosed chronic pancreatitis (CP) was measured. The concentration of interleukin-6 and metallothionein was determined by means of ELISA and the radioisotopic method, respectively. The enzyme activities in the fluid were assayed by the colorimetric method. Samples of tissues of normal pancreas (n = 4) and CP (non-smoking n = 7; smoking n = 12) were verified histopathologically and then IL-6, MT and enzymes were localized by immunohistochemical staining using the monoclonal anti-human antibody. ResultsThe concentrations of metallothionein and interleukin-6 were significantly higher in smoking patients with CP (as compared with the non-smoking population (p < 0.01; p < 0.001). Interestingly, the ratio of MT/IL-6 in smoking patients with CP was reduced in comparison to non-smoking patients (respectively: 1.1; 5.6). In smoking patients, a significant elevation of the Cu/Zn SOD and GPx activities was revealed as compared with the non-smokers (p < 0.04; p < 0.0007). These studies clearly demonstrate a moderate and strong expression of IL-6 and enzymes in acinar, islet and duct cells of smoking patients. ConclusionsThese observations favor the role of the oxidative stress in the induction of pancreatitis associated with chronic cigarette smoke inhalation.

Addition of açaí ( Euterpe oleracea) to cigarettes has a protective effect against emphysema in mice

Chronic inhalation of cigarette smoke (CS) induces emphysema by the damage contributed by oxidative stress during inhalation of CS. Ingestion of açai fruits ( Euterpe oleracea) in animals has both antioxidant and anti-inflammatory effects. This study compared lung damage in mice induced by chronic (60-day) inhalation of regular CS and smoke from cigarettes containing 100 mg of hydroalcoholic extract of açai berry stone (CS + A). Sham smoke-exposed mice served as the control group. Mice were sacrificed on day 60, bronchoalveolar lavage was performed, and the lungs were removed for histological and biochemical analyses. Histopathological investigation showed enlargement of alveolar space in CS mice compared to CS + A and control mice. The increase in leukocytes in the CS group was higher than the increase observed in the CS + A group. Oxidative stress, as evaluated by antioxidant enzyme activities, mieloperoxidase, glutathione, and 4-hydroxynonenal, was reduced in mice exposed to CS + A versus CS. Macrophage and neutrophil elastase levels were reduced in mice exposed to CS + A versus CS. Thus, the presence of açai extract in cigarettes had a protective effect against emphysema in mice, probably by reducing oxidative and inflammatory reactions. These results raise the possibility that addition of açaí extract to normal cigarettes could reduce their harmful effects.

Evidence for cigarette smoke-induced oxidative stress in the rat pancreas

Background/aims: Recent findings with a rodent model of cigarette smoke inhalation revealed a causal relationship between chronic exposure to cigarette smoke and the development of pancreatitis. The present study was conducted to ascertain whether cigarette smoke induces oxidative stress in the rat pancreas concurrently with inflammation.Methodology: Rats (six per treatment group) were treated for 0, 3, 6, 9, or 12 weeks with cigarette smoke (0.7 mg/L). Pancreatic tissues were examined for histological and pathological alterations and serum for changes in interleukin-6 concentration. Pancreatic expression and localization of α-smooth muscle actin, transforming growth factor-β1, and collagen-1 were determined as measures of progressive inflammation/fibrosis. Pancreatic superoxide dismutase and glutathione peroxidase activities and malondialdehyde content were measured as indices of oxidative stress.Results: Inflammatory cell infiltration and ductal hyperplasia were detected in pancreata after 12 weeks of treatment with cigarette smoke. The serum interleukin-6 concentration increased significantly and pancreatic glutathione peroxidase activity declined significantly after 12 weeks of treatment. No other significant changes were observed.Conclusions: Pancreata of rats exposed chronically to cigarette smoke exhibit inflammation concurrently with suppression of glutathione peroxidase activity. These observations favor a role for oxidative stress in the induction of pancreatitis associated with chronic cigarette smoke inhalation.

Targeted Induction of Lung Endothelial Cell Apoptosis Causes Emphysema-like Changes in the Mouse

Pulmonary gas exchange relies on a rich capillary network, which, together with alveolar epithelial type I and II cells, form alveolar septa, the functional units in the lung. Alveolar capillary endothelial cells are critical in maintaining alveolar structure, because disruption of endothelial cell integrity underlies several lung diseases. Here we show that targeted ablation of lung capillary endothelial cells recapitulates the cellular events involved in cigarette smoke-induced emphysema, one of the most prevalent nonneoplastic lung diseases. Based on phage library screening on an immortalized lung endothelial cell line, we identified a lung endothelial cell-binding peptide, which preferentially homes to lung blood vessels. This peptide fused to a proapoptotic motif specifically induced programmed cell death of lung endothelial cells in vitro as well as targeted apoptosis of the lung microcirculation in vivo. As early as 4 days following peptide administration, mice developed air space enlargement associated with enhanced oxidative stress, influx of macrophages, and up-regulation of ceramide. Given that these are all critical elements of the corresponding human emphysema caused by cigarette smoke, these data provide evidence for a central role for the alveolar endothelial cells in the maintenance of lung structure and of endothelial cell apoptosis in the pathogenesis of emphysema-like changes. Thus, our data enable the generation of a convenient mouse model of human emphysema. Finally, combinatorial screenings on immortalized cells followed by in vivo targeting establishes an experimental framework for discovery and validation of additional ligand-directed pharmacodelivery systems.

State of the Art. Cellular and Molecular Mechanisms of Alveolar Destruction in Emphysema: An Evolutionary Perspective

Emphysema consists of a unique pattern of alveolar destruction, resulting in marked airspace enlargement with reduction of alveolar capillary exchange area. Classical concepts of the pathogenesis of emphysema have relied on the paradigm set by the inflammation and protease/antiprotease imbalance. We propose herein that cigarette smoke constitutes an environmental hazard that causes alveolar destruction by the interaction of apoptosis, oxidative stress, and protease/antiprotease imbalance. We draw a parallel between organismal aging, organ structural maintenance, and the damage resulting from chronic cigarette smoke inhalation. The stochastic interaction between environmental hazards and the effort of an organism or a particular organ to fend off these hazards results in the accumulation of cellular damage and features characteristic of aging. Inflammation follows as the result of the multiplication of injuries. We highlight the importance of understanding the biology of the interaction of alveolar cells in homeostasis and in alveolar destruction, and the potential role of novel processes related to senescence and stress response. An evolutionary perspective of emphysema that incorporates mechanisms related to aging may lead to important advances in the understanding and therapeutic targeting of chronic obstructive pulmonary disease.

Efeitos da inalação passiva da fumaça de cigarro sobre as pregas vocais de ratos

Poucos estudos demonstram as reações patológicas devidas à inalação de fumaça pelas vias aéreas de ratos. OBJETIVO: Estudar e analisar os possíveis efeitos histopatologicos produzidos pela inalação crônica de fumaça de cigarro nas pregas vocais de ratos. DESENHO DE ESTUDO: Experimental. MATERIAL E MÉTODOS: 36 ratos masculinos (Rattus norvergicus Wistar), de 60 dias de idade, foram mantidos em gaiolas e expostos à inalação da fumaça produzida por 10 cigarros, 3 vezes ao dia, 7 dias por semana, para períodos de 25, 50 e 75 dias, e os controles respectivos. Os animais foram sacrificados e as suas laringes dissecadas e submetidas a análise histológica com coloração de Hematoxilina e Eosina e analisados através de microscopia simples. RESULTADOS: Os ratos expostos ao cigarro exibiram menor (p &lt;0,05) massa corporal que o grupo controle. Havia hiperplasia e metaplasia escamosa na extremidade livre da prega vocal e hiperplasia escamosa na porção mediana da prega vocal em todos os 3 períodos de estudo. Além disso, o grupo de 50 dias revelou metaplasia com queratinização nesta área. Não foram observadas alterações morfológicas em outras áreas da laringe e reação inflamatória da lâmina propria. CONCLUSÃO: Foi concluído que a inalação passiva de fumaça de cigarro rende mudanças morfológicas importantes no epitélio da prega vocal que podem, eventualmente, progredir para neoplasia.

Effects of passive smoke inhalation on the vocal cords of rats

SummaryFew studies have demonstrated the pathologic reactions yielded by smoke inhalation on the airway in rats. Aim: The aim of this study was to analyze the possible histopathological effects produced by chronic cigarette smoke inhalation on the vocal folds of rats. Study design: Experimental. Material and Method: 36 male rats (Rattus norvergicus Wistar strain), aged 60 days, were kept in cages and exposed to inhalation of the smoke produced by 10 cigarettes lit 3 times a day, 7 days a week, for periods of 25, 50 and 75 days, and their respective controls. Thereafter the animals were killed and their larynxes were dissected and submitted to histological processing for achievement of histological sections, which were stained with Hematoxylin and Eosin and analyzed by light microscopy. Results: The rats exposed to smoke displayed smaller (p< 0,05) body mass than the control group. There was hyperplasia and squamous metaplasia in the free edge of the vocal fold and squamous hyperplasia on the middle portion of the vocal fold in all 3 study periods. Moreover, the 50-day group revealed keratinizing metaplasia in this area. Morphological alterations in other areas of the larynx and inflammatory reaction of the lamina propria were also not observed. Conclusion: It was concluded that the passive inhalation of cigarette smoke yields important morphological changes in the vocal fold epithelium, which may progress to neoplasia.

Genetic polymorphisms and environmental risk of lung cancer: a review.

Lung cancer results from man-made and natural environmental exposures acting in concert with both genetic and acquired characteristics. Chronic inhalation of cigarette smoke is a major risk factor, and environmental tobacco exposure can cause lung cancer in life-long neversmokers. Air pollution, indoor-radon exposure, occupational exposures, dietary, physical activity, and reproductive history have been identified as independent or contributing risk factors for lung cancer. Because only a small portion of smokers develops the disease, genetic susceptibility can contribute to the risk. Developments in molecular biology have led to the discovery of biological markers that increase predisposition to lung carcinogenesis. Therefore, the high-risk genotype of an individual can be determined easily. Because of the great number of carcinogen-activating and -detoxifying enzymes, the variation in their expression, the complexity of exposures to tobacco carcinogens, and the existence of multiple alleles at loci of those enzymes results in differential susceptibilities of individuals. As lung cancer is a multifactorial disease, an improved understanding of the interplay of environmental and genetic polymorphisms at multiple loci can help identify individuals who are at increased risk for lung cancer. Hopefully, in the future we will be able to screen for lung cancer susceptibility by using specific biomarkers.

Genetic polymorphism of enzymes involved in xenobiotic metabolism and the risk of lung cancer.

Chronic inhalation of cigarette smoke is a major risk factor for the development of lung cancer. It has been suggested that genetic susceptibility may contribute to the risk, because only a small portion of smokers develops the disease. Several polymorphisms that involve the metabolic activation or detoxification of carcinogens derived from cigarette smoke have been found to be associated with lung cancer risk. Many studies have focused on the relation between the distribution of polymorphic variants of different forms of the metabolic enzymes and lung cancer susceptibility. In this respect two groups of genetic polymorphisms of enzymes involved in xenobiotic metabolism, cytochrome P450 (CYP) and glutathione S-transferases (GSTs), have been discussed.CYP multigene superfamily consists of 10 subfamilies (CYP1-CYP10). A positive association between development of lung cancer and the mutant homozygous genotype ofCYP1A1 gene has been reported in several Japanese populations but such an association has not been observed in either Caucasians or African-Americans. The relation betweenCYP2D6 and lung cancer remains conflicting and inconclusive. Several polymorphisms have been identified at theCYP2E1 locus. No definitive link between the polymorphisms ofCYP2E1 and the risk of lung cancer has, however, been identified. The role of otherCYP2 isoforms in lung carcinogenesis has not been sufficiently investigated.GSTs form a superfamily of genes consisting of five distinct families, namedGSTA, GSTM, GSTP, GSTT andGSTS. The role ofGSTM, GSTT1 orGSTP1 polymorphism in modifying the lung cancer risk may be more limited than has been so far anticipated.Although some genetic polymorphisms discussed here have not shown significant increases/decreases in risk, individuals with differing genotypes may have different susceptibilities to lung cancer. Hopefully, in future studies it will be possible to screen for lung cancer using specific biomarkers.

Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice.

To determine which proteinases are responsible for the lung destruction characteristic of pulmonary emphysema, macrophage elastase-deficient (MME-/-) mice were subjected to cigarette smoke. In contrast to wild-type mice, MME-/- mice did not have increased numbers of macrophages in their lungs and did not develop emphysema in response to long-term exposure to cigarette smoke. Smoke-exposed MME-/- mice that received monthly intratracheal instillations of monocyte chemoattractant protein-1 showed accumulation of alveolar macrophages but did not develop air space enlargement. Thus, macrophage elastase is probably sufficient for the development of emphysema that results from chronic inhalation of cigarette smoke.

Effect of age on alteration of glutathione metabolism following chronic cigarette smoke inhalation in mice.

Cigarette smoke is the most common oxidant stress in daily life and may affect the antioxidant capacity in humans and animals. The antioxidant functions may play an important role in preventing age-related disorders. However, influences of chronic cigarette smoke on the antioxidant capacity of visceral organs have not been investigated in the age. Senescene-accelerated mice (SAM) are good models for studying physiologic and/or pathologic aging. A senescene-prone strain, SAMP2, shows characteristics of premature aging. The senescence-resistant strain, SAMR1, exhibits relatively normal aging. In this study we examined the effects of chronic cigarette smoke exposure on the glutathione (GSH) metabolism of visceral organs in the two strains of mice that were 6 and 18 months old. After a 4-week cigarette or air exposure, total GSH and oxidized GSH (GSSG) in the organs were examined. In the young (6-month-old) mice, exposure to cigarette smoke caused a significant decrease of GSH in liver, blood, and lung of SAMP2 but not in those of SAMR1. In the aged (18-month-old) mice reduced GSH with a marked increase of GSSG were found in liver of both strains of SAM following cigarette smoke exposure. The baseline values of GSH and the GSSG/GSH ratio after air exposure were slightly changed with age, and the values after exposure to cigarette smoke were changed markedly with advancing age. These results indicate that GSH metabolism may be impaired by chronic cigarette smoke exposure in mice and that aged mice are more susceptible to cigarette smoke than young mice.

Lack of Elevation of Stress-Inducible Heat-Shock Protein 70 in the Ferret Lung After Chronic Cigarette Smoke Inhalation

AbstractFew investigations have examined in vivo expression of lung heat-shock proteins (HSPs) following environmental stress. This study was performed to ascertain if stress-inducible HSP 70 in the ferret lung is elevated following inhalant exposure to 2 high concentrations of a mixture of mainstream and sidestream cigarette smoke: (a) 381 ± 97 (SD) mg/m3 and (b) 38.2 ± 13.3 (SD) mg/m3. Ferrets (n = 5 for each concentration) starting at 5 wk of age were exposed head-only to cigarette smoke for 2 h/day, 5 days/wk for a total of 15 wk; control ferrets (n = 4) were exposed to filtered air. Samples of the peripheral lung from the right apical lobe were obtained for analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), protein immunoblotting, and subsequent chemiluminescent detection. Results revealed that stress-inducible HSP 70 is present constitutively in the control ferret lung and is not elevated significantly (p = .7758) in lungs from both groups of smoke-exposed ferrets.

A role of aryl hydrocarbon hydroxylase inducibility in susceptibility to lung carcinogenesis

Lung cancer mortality has been increasing rapidly in recent years in Japan and is expected to exceed that of stomach cancer in male Japanese in the near future. Although chronic inhalation of cigarette smoke is a major risk factor for the development of lung cancer, it seems important to examine genetic susceptibility to the disease as well. Aryl hydrocarbon hydroxylase (AHH), a drug-metabolism enzyme, is useful in determining the individual differences in genetic susceptibility to lung carcinogenesis. AHH is a microsomal membrane-bound monooxygenase system located in most tissues of the body. In mice, AHH inducibility is under the control of the Ah locus and certain inbred strains of mice are susceptible to AHH induction by 3-methylcholanthrene treatment (Ah responsive strains), while other strains are not (Ah non-responsive strains). A strong correlation was observed between AHH inducibility and tumor incidence in mice. Since AHH is also responsible for the activation to carcinogens of benzo (a)pyrene and other aromatic hydrocarbons in cigarette smoke, it may also be important in humans in the causation of lung cancer. Kellermann et al. investigated the genetics of AHH in a human population and reported that the inducibility of this enzyme was controlled by a single gene locus with 2 dominant alleles. They classified humans as having low, intermediate, or high inducibility of AHH. In addition, they reported a significant positive correlation between the extent of inducibility and susceptibility to lung cancer. Their claim, however, has been both supported and refuted by subsequent investigators. Recently, a close association between development of lung cancer and three polymorphisms of CYP1A1 caused by the presence or absence of one MspI site in the 3'-flanking region, namely, a predominant homozygote pattern (A), a heterozygote pattern (B) and a homozygous rare allele pattern (C), has been reported. The relationship between AHH inducibility and polymorphisms of CYP1A1 had not been investigated previously. Our study indicated that the genotype of C, very frequent in Kreyberg type I, was closely related to high AHH inducibility. Thus, the relationship between AHH inducibility and lung cancer, suggested by Kellermann et al., is supported by our study. Further studies will be needed to confirm the present results. Identification of smokers who have genetically high susceptibility to lung cancer (pattern C), may become important for the prevention of lung cancer.

Tobacco smoke suppresses T cells but not antigen-presenting cells in the lung-associated lymph nodes

Chronic inhalation of cigarette smoke in mice preferentially inhibited the antigen-specific T-cell proliferative response of lung-associated lymph nodes compared to anatomically distant lymph nodes. Cell mixing experiments demonstrated that the defect in smoked mice resulted from an abnormality in T-lymphocyte function. In contrast, the activity of antigen-presenting cells was similar in smoked and sham-smoked control animals. These results suggest that T-cell function in lung-associated lymphoid tissue may be inhibited in smokers, leading to a localized predisposition to respiratory tract infections.