Frequencies of chromosome aberrations in a control population determined by G banding

Control data on chromosome aberration frequencies determined by G banding from several studies undertaken in this laboratory have been re-analysed in relation to age and smoking. The combined study group comprised a total of 162 men (90 non-smokers and 72 smokers) with ages ranging from 20 to 72 years. For the group as a whole, significant increases were observed in translocations and all symmetrical exchanges with increasing age and also when smokers were compared with non-smokers.     

Analysis of chromosomal aberration frequencies in the peripheral blood lymphocytes of smokers exposed to uranyl compounds

One hundred fifteen smokers working in a nuclear fuel manufacturing facility were analysed for various types of chromosomal aberrations. They experienced exposure for a period of 1-25 years. Their age ranges from 23 to 52 years. A total of 94 smokers and 118 non-smokers who were not exposed to uranyl compounds or to any other known mutagens and belong to the same age group formed the control subjects. The results showed that there is a significant increase in the frequency of chromosomal aberrations in the exposed smokers when compared to the control smokers. In the control group, the smokers showed a high frequency of chromosomal aberrations when compared to non-smokers suggesting clastogenic effect of smoking. Chromosomal aberrations observed in the exposed smokers could be due to the cumulative effect of both smoking and exposure to uranyl compounds.     

Differential enhancement of sister-chromatid exchange frequencies by alpha-naphthoflavone in cultured lymphocytes from smokers and non-smokers

The sister-chromatid exchange (SCE) frequency was assessed in peripheral lymphocytes from 4 smokers and 8 non-smokers in the absence or presence of alpha-naphthoflavone (ANF) in the culture media. ANF produced a concentration-dependent increase in the frequency of SCEs in smoking individuals. At an ANF concentration of 11 micrograms/ml, average SCE levels were 54% and 13% above the baseline levels in smokers and non-smokers, respectively. The ANF-enhanced increase in the SCE frequency ranged from 3.12 to 5.72 among smokers, and from 0 to 1.96 among the non-smokers. No significant difference in the mean SCE baseline levels between smokers and non-smokers was detected. The mechanism responsible for the enhanced frequency of SCEs in smokers following in vitro exposure to ANF is not clear, but may reflect changes in metabolic activation/deactivation or increased sensitivity to genetic effects of ANF.     

Increased local matrix metalloproteinase-8 expression in the periodontal connective tissues of smokers with periodontal disease

Matrix metalloproteinase (MMP)-8 has been associated with the progression of periodontitis, a common inflammatory disease of the supporting structures of the teeth, and with other degradative diseases. Tobacco smokers are at high risk of developing periodontitis that may progress more rapidly and respond poorly to treatment. Therefore, MMP-8 expression was determined by immunofluorescence staining in 60 random, computer-selected fields in the excised periodontal tissues of smokers and non-smokers, balanced for age, gender, and periodontal status. Immunofluorescence intensity, representing MMP-8 expression, in the periodontal tissues of smokers (30 fields from 6 subjects, mean 1154+/-124 units) was significantly higher than that in the periodontal tissues of non-smokers (30 fields from 6 subjects, mean 817+/-60 units; p < 0.05). Serum MMP-8 concentrations were measured by ELISA and compared in a larger group of smokers (n = 20) and age- and gender-balanced non-smokers (n = 20). Systemic MMP-8 concentrations in smokers and non-smokers were not significantly different (p > 0.05). A local tobacco-related increase in MMP-8 burden may contribute to periodontal disease progression in tobacco smokers. This finding may also have relevance to other tobacco-induced inflammatory diseases, such as vascular and pulmonary diseases.     

Analysis of chromosomal aberrations in men occupationally exposed to cement dust

Cement industry is considered as a major pollution problem on account of dust and particulate matter emitted at various steps of cement manufacture. Cement dust consists of many toxic constituents. The workers who are employed in cement industries are exposed to cement dust for long periods. Therefore, it is mandatory to evaluate the mutagenic effects of occupational exposure to cement dust in such workers. In the present study, we analyzed the samples of 124 male workers including 59 smokers and 65 non-smokers who were employed in cement industry for a period of 1–17 years. For comparison, 106 controls (including 47 smokers and 59 non-smokers) of the same age group and socio-economic status were also studied. Controls had no exposure to cement dust or any known physical or chemical agent. A significant increase in the incidence of chromosomal aberrations was observed in the exposed group when compared to the control group. The results were analyzed separately for non-smokers and smokers. The chromosomal damage was more pronounced in the smokers when compared with the non-smokers both in control and exposed groups. A significant increase in the frequency of chromosomal aberrations was also observed with increase in age in both control and exposed subjects.     

Analysis of chromosomal aberrations in men occupationally exposed to cement dust

Cement industry is considered as a major pollution problem on account of dust and particulate matter emitted at various steps of cement manufacture. Cement dust consists of many toxic constituents. The workers who are employed in cement industries are exposed to cement dust for long periods. Therefore, it is mandatory to evaluate the mutagenic effects of occupational exposure to cement dust in such workers. In the present study, we analyzed the samples of 124 male workers including 59 smokers and 65 non-smokers who were employed in cement industry for a period of 1-17 years. For comparison, 106 controls (including 47 smokers and 59 non-smokers) of the same age group and socio-economic status were also studied. Controls had no exposure to cement dust or any known physical or chemical agent. A significant increase in the incidence of chromosomal aberrations was observed in the exposed group when compared to the control group. The results were analyzed separately for non-smokers and smokers. The chromosomal damage was more pronounced in the smokers when compared with the non-smokers both in control and exposed groups. A significant increase in the frequency of chromosomal aberrations was also observed with increase in age in both control and exposed subjects.     

Factors of humoral resistance in workers exposed to vinyl chloride with a view to smoking habits

Serum samples were assayed in 110 workers (59 smokers and 51 non-smokers) at PVC manufacturing factory, the results being compared with those obtained in a group of age-matched healthy controls. Non-smokers had significantly higher levels of immunoglobulins (IgG, IgA, IgM), while in smokers there was an increase in IgM only. Lysozyme levels (LYS) were elevated in all exposed subjects, but there was a highly significant decrease in the total protein (TP) content. Alfa-2-macroglobulin (A2M) and orosomucoid (ORO) were also elevated in exposed workers. A significant increase was found in ceruloplasmin (CPL), with smokers having higher levels than non-smokers. No difference was detected between the examined groups in transferrin (TRF) and alfa-1-antitrypsin (A1AT). Exposure duration did not correlate with any of the assayed parameters. The positive correlation of IgA levels and inverse correlation of CPL with age in the control group could not be confirmed in the exposed subjects where a significant inverse correlation between age and AlAT levels, which was found to be positive in exposed non-smokers, proved to be inverse in the subgroup of smokers. The authors discuss possible explanations of the reported findings.     

A meta-analysis of cigarette smoking,bone mineral density and risk of hip fracture: recognition of a major effect.

OBJECTIVE: To determine the magnitude and importance of the relation between smoking, bone mineral density, and risk of hip fracture according to age. DESIGN: Meta-analysis of 29 published cross sectional studies reporting the difference in bone density in 2156 smokers and 9705 non-smokers according to age, and of 19 cohort and case-control studies recording 3889 hip fractures reporting risk in smokers relative to non-smokers. RESULTS: In premenopausal women bone density was similar in smokers and non-smokers. Postmenopausal bone loss was greater in current smokers than non-smokers, bone density diminishing by about an additional 2% for every 10 year increase in age, with a difference of 6% at age 80. In current smokers relative to non-smokers the risk of hip fracture was similar at age 50 but greater thereafter by an estimated 17% at age 60, 41% at 70, 71% at 80, and 108% at 90. These estimates of relative risk by age, derived directly from a regression analysis of the studies of smoking and hip fracture, were close to estimates using the difference in bone density between smokers and non-smokers and the association between bone density and risk of hip fracture. The estimated cumulative risk of hip fracture in women in England was 19% in smokers and 12% in non-smokers to age 85; 37% and 22% to age 90. Among all women, one hip fracture in eight is attributable to smoking. Limited data in men suggest a similar proportionate effect of smoking as in women. The association was not explained by smokers being thinner, younger at menopause, and exercising less nor by actions of smoking on oestrogen, but smoking may have a direct action on bone. CONCLUSIONS: Hip fracture in old age is a major adverse effect of smoking after the menopause. The cumulative excess bone loss over decades is substantial, increasing the lifetime risk of hip fracture by about half.     

Down-regulation of circulating microRNA let-7a in Egyptian smokers

Altered miRNAs were associated with cigarette smoking. The study aimed to examine the gene expression level of plasma let-7a among healthy smokers and compared it with the non-smokers. Forty subjects were recruited for the present study and classified into 21 smokers and 19 non-smokers, age, and sex were matched. The software that used to design functional primers was MIRprimer. Quantitative real-time PCR was employed to compare the relative expression of plasma let-7a. Results showed that the level of let-7a was down-regulated in smokers to 0.34fold (p?=?0.006) that of the non-smokers. Plasma let-7a showed an area under curve (AUC) of 0.749 with sensitivity 43% and specificity 100%. In conclusion, plasma let-7a was significantly down-regulated in the smokers, and it might be considered a candidate biomarker to discriminate between smokers and non-smokers.     

Does breathing other people's tobacco smoke cause lung cancer?

The available epidemiological studies of lung cancer and exposure to other people''s tobacco smoke, in which exposure was assessed by whether or not a person classified as a non-smoker lived with a smoker, were identified and the results combined. There were 10 case-control studies and three prospective studies. Overall, there was a highly significant 35% increase in the risk of lung cancer among non-smokers living with smokers compared with non-smokers living with non-smokers (relative risk 1.35, 95% confidence interval 1.19 to 1.54). Part of this increase was almost certainly caused by the misclassification of some smokers as non-smokers. As smokers, who are more likely to get lung cancer than non-smokers, tend to live with smokers this misclassification probably exaggerated the estimated increase in risk. Adjustment for this error reduced the estimate to 30% (relative risk 1.30), but as people who live with non-smokers may still be exposed to other people''s smoke this estimate was revised again to allow for the fact that a truly unexposed reference group was not used. The increase in risk among non-smokers living with smokers compared with a completely unexposed group was thus estimated as 53% (relative risk of 1.53). This analysis, and the fact that non-smokers breathe environmental tobacco smoke, which contains carcinogens, into their lungs and that the generally accepted view is that there is no safe threshold for the effect of carcinogens, leads to the conclusion that breathing other people''s tobacco smoke is a cause of lung cancer. About a third of the cases of lung cancer in non-smokers who live with smokers, and about a quarter of the cases in non-smokers in general, may be attributed to such exposure.     

Human urine mutagenicity study comparing cigarettes which burn or only heat tobacco

Cigarette smokers have been reported to void urine which is more mutagenic, as measured in the Ames bacterial mutation assay, than urine voided by non-smokers. Condensate from the mainstream smoke of a cigarette which heats, but does not burn tobacco (test cigarette) showed no evidence of mutagenicity in a battery of in vitro genotoxicity assays under conditions in which condensate from the mainstream smoke of cigarettes that burn tobacco was mutagenic. The objective of this study was to determine whether the absence of mutagenic activity observed in the in vitro assays would be reflected in the urine of smokers of the test cigarette. 72 subjects (31 smokers and 41 non-smokers) were enrolled in a 6-week study, with the smokers randomly divided into 2 groups. The study was designed as a double crossover, with each smoker smoking both test (tobacco-heating) and reference (tobacco-burning) cigarettes. This design allowed each smoker to serve as his or her own control while at the same time allowing comparisons between groups of non-smokers and smokers of both test and reference cigarettes. 24-h urine samples were collected twice a week and concentrated using XAD-2 resin. Urine concentrates were tested in Ames bacterial strains TA98 and TA100, with and without metabolic activation and with and without beta-glucuronidase/aryl sulfatase. Individuals who smoked the test cigarette voided urine which was significantly less mutagenic than that voided when they smoked reference cigarettes. The mutagenicity of urine from smokers who smoked the test cigarette and non-smokers did not differ under any of the assay conditions used in this study.     

Nasal carriage of methicillin-resistant Staphylococcus aureus among smokers and cigarette factory workers

Effects of smoking and tobacco on nasal carriage and colonisation rates of Staphylococcus aureus were investigated on 368 healthy males aged between 30 and 40 years old. The study group comprised 100 non-smokers (control group), 91 smokers, and 177 cigarette factory workers (42 smokers, 135 non-smokers). Quantitative cultures were done from the nasal swabs of all participants. After identification and determination of colony counts, S. aureus strains were tested for methicillin resistance using the oxacillin disk diffusion method. The rates of nasal carriage of S. aureus were found to be 30% in the control group, 33% in smokers, and 41% in cigarette factory workers. Overall, S. aureus colonisation (> or = 500 cfu/ml) was detected in 72% of the carriers (55/76). Colonisation rates were 43%, 63%, and 85% in the carriers of the study groups, respectively. An increasing colonisation rate was detected in accordance with the increasing number of cigarettes smoked per day, and smoking period. While methicillin-resistant Staphylococcus aureus was only found in 3% of the 30 S. aureus strains isolated from the control group, its isolation rate was 20% in the 30 S. aureus isolates of the smokers, and 33% in the 72 S. aureus isolates of the cigarette factory workers. These results indicate that cigarette and/or tobacco appear to have noticeable effects on the ecology of the nose.     

Reference levels of the tumor markers carcinoembryonic antigen, the carbohydrate antigens 19-9 and 72-4, and cytokeratin fragment 19 using the Elecsys Relecsys 1010 analyzer in a normal population in Kuwait. The importance of the determination of local reference levels

The tumor markers CEA, CA 19-9, CA 72-4 and CYFRA 21-1 were analyzed in a group of apparently healthy subjects (n=232) in Kuwait using the Elecsys Relecsys 1010 analyzer. The distribution of the tumour marker levels was analyzed separately in Kuwaitis (n=103), non-Kuwaitis (n=129), smokers (n=68), non-smokers (n=164), males (n=138) and females (n=94). The distribution of CEA was significantly different in Kuwaitis vs. non-Kuwaitis in the total population (p=0.033) and in non-smokers (p=0.049); in males vs. females in the total population (p<0.0001) and in non-smokers (p=0.0002); and in smokers vs. non-smokers in the total population (p<0.0001) using the non-parametric Mann-Whitney U test. None of the other tumour markers showed significant differences in the subgroups. The upper reference level was defined as the 95th percentile of the normal values in each group. A higher reference level of CEA was observed in smokers (vs. non-smokers) in the total population. Also higher reference levels of CEA were observed in males (vs. females) both in the total population and in non-smokers. In the total population the respective reference levels were: CEA: 4.4 microg/L, CA 19-9: 35 kU/L, CA 72.4: 2.4 kU/L, and CYFRA 21.1: 2.1 microg/L. These results were compared with data in the kit inserts and literature data. The impact of 95th percentiles in a local heterogeneous population is discussed.     

Mitochondrial DNA mutations in the parotid gland of cigarette smokers and non-smokers

It has previously been demonstrated that mitochondrial DNA (mtDNA) mutations accumulate in the lung and increase in frequency with age. It has also been shown that the level of mtDNA mutations including deletions and base substitutions are elevated in lung tissue of smokers relative to non-smokers. We have previously shown that the 'common' 4977 bp mtDNA deletion is present in the parotid (salivary) gland of smokers and non-smokers and that there is a significant increase in the level of this deletion in Warthins tumour, an oncocytoma of the parotid gland. In this study we used semi-quantitative PCR to confirm the presence of 4977 bp mtDNA deletion in the parotid gland of non-smokers and smokers. Importantly, we show that the deletion accumulates with age regardless of smoking status and that there was no significant difference in the level of the 4977 bp deletion in parotid tissue of smokers and non-smokers. Using strand conformational polymorphism (SSCP) and direct sequencing we also found 5/23 smokers had parotid tissue specific base substitutions: either an A/T to G/C transition at A4767 or a G/C to A/T transition at G4853. These results are evidence of age related increase in the 4977 bp deletion and a higher level of mutations, probably due to oxidative damage, in the parotid gland of smokers.     

Products of 5-lipoxygenase and myeloperoxidase activities are increased in young male cigarette smokers

Abstract The significance of 5-lipoxygenase and myeloperoxidase activities has not been extensively studied among young male smokers. Leukotriene B(4), 20-hydroxy-leukotriene B(4), 20-carboxy-leukotriene B(4) and 3-chlorotyrosine were measured in plasma and urinary samples of young male smokers at 8 hours following cigarette abstinence and an hour after cigarette smoking. Leukotriene B(4) and 3-chlorotyrosine were determined in neutrophils isolated from these individuals. The levels of these markers were compared with those of age-matched controls. In vitro studies were performed to evaluate the production of leukotriene B(4) and 3-chlorotyrosine from human neutrophils following exposure to nicotine and cotinine. Thirty male smokers (mean age, 27.4 years) and 28 male non-smokers (mean age, 28.7 years) were studied. Plasma levels of leukotriene B(4), 20-carboxy-leukotriene B(4) and 3-chlorotyrosine were higher in smokers than in non-smokers; leukotriene B(4) and 20-carboxy-leukotriene B(4) levels increased further an hour after cigarette smoking. Peripheral neutrophils isolated from smokers showed greater expressions of myeloperoxidase and 5-lipoxygenase activities compared with non-smokers, while plasma leukotriene B(4) and 3-chlorotyrosine were correlated significantly with high-sensitivity C-reactive protein and plasma nicotine concentrations. Exposure of human neutrophils to nicotine and cotinine resulted in a higher production of leukotriene B(4) and 3-chlorotyrosine. To conclude, leukotriene B(4) and 3-chlorotyrosine levels are increased in young male cigarette smokers. These results suggest that cigarette smoking aggravates neutrophil-mediated inflammation by modulating the activities of myeloperoxidase and 5-lipoxygenase pathways.     

Study of the amniotic fluid from smokers and non-smokers in the Ames test

Amniotic fluid from smokers and non-smokers was tested by the Salmonella/mammalian microsome test. Concentrated amniotic fluid from heavy smokers at term showed an increase in the number of revertants with increasing exposure to tar. However, some of the non-smokers had a higher number of revertants than the smokers. No significant differences were found between second-trimester samples from smokers and non-smokers, but the limited volumes available at this stage of pregnancy may be a source of error.     

Smoking in pregnancy: associations with skinfold thickness,maternal weight gain,and fetal size at birth.

Skinfold thickness is an index of subcutaneous fat, and certain maternal conditions during pregnancy affect the skinfold thicknesses of the baby. A study was performed to investigate the effect of smoking on skinfold thickness, maternal weight gain, and fetal size at birth. A total of 452 mothers with normal singleton pregnancies were groups as: non-smokers, light-to-moderate smokers, or heavy smokers. Maternal age, height, parity, and duration of pregnancy were similar in the three groups. Heavy smokers gained significantly less weight than non-smokers, but there was no significant difference in skinfold thickness. Babies born to smokers had lower birth weights and smaller head circumferences and were shorter than those born to non-smokers, but skinfold thicknesses were similar. The presence of a normal layer of subcutaneous fat in babies whose mothers smoked suggests that fetal growth retardation is not caused by nutritional deficiencies.     

Aluminium, Cadmium and Lead Concentration in the Hair of Tobacco Smokers

In the research, the contents of heavy metals, Al, Cd and Pb, in the hair of individuals who reside in similar environmental conditions were spectrometrically determined with the use of atomic emission spectrometry–inductively coupled plasma spectrophotometer. The relation to their tobacco smoking habit, age and sex was established. It was observed that the level of all three determined elements was generally higher in the hair of smokers in comparison to hair of non-smokers in both younger and older age groups. In addition, it has been observed that, in the group of elderly people over 50 years old, there was an increase in the content of aluminium, cadmium and lead both in smokers and non-smokers, irrespective of their sex. The sex-related differences in the content of the investigated elements were not unidirectional, and only in few cases did they reveal statistical significance.     

Serum Clara cell protein (CC16) in healthy young smokers

The CC16 microprotein is the main secretory product of Clara cells, which are epithelial cells lining lung airways. In crossing through the bronchoalveolar/blood barrier, CC16 diffuses passively into plasma. Serum CC16 (sCC16) has recently been proposed as a biomarker for detecting Clara cell impairments. The aim of this study was to assess if sCC16 concentrations are reduced in a group of healthy young smokers. A group of 118 healthy young males volunteered to take part in the study. Each subject answered a questionnaire, and provided blood and urine samples. Serum CC16, urinary cotinine and creatinine were measured. Median serum CC16 concentrations were lower in smokers than in non-smokers (11.3 mug l^-1 vs 14.6 mug l^-1; p = 0.005; N = 89 and 29, respectively) but did not correlate with either the daily or the life-time cigarette consumption, or with urinary cotinine concentrations. sCC16 did not correlate with age or body mass index in the whole study population or in the groups of smokers and non-smokers. These results suggest the reduction in sCC16 concentrations in a group of healthy young smokers may be an early effect of cigarette smoking.     

Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial

Background

KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD). Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history.

Methods

The concentrations of KL-6 in plasma and induced sputum supernatants from young and/or middle aged/elderly non-smokers, smokers and patients with COPD were assayed by ELISA (n = 201). The subjects were classified into five groups according to age, smoking status and presence of COPD. In addition, KL-6 expression in control and diseased lung i.e. samples from patients with COPD (n = 28), were analyzed by immunohistochemistry and digital image analysis.

Results

The plasma levels of KL-6 increased with age both in non-smokers and smokers. Among middle aged/elderly subjects, plasma KL-6 levels in all smokers regardless of COPD were significantly higher than in non-smokers, whereas sputum levels of KL-6 were significantly higher in COPD compared not only to non-smokers but also to smokers. KL-6 was more prominently expressed in the bronchiolar/alveolar epithelium in COPD than in the control lungs. Plasma and sputum KL-6 levels correlated inversely with obstruction and positively with smoking history and ageing. The linear multiple regression analysis confirmed that age and cigarette smoking had independent effects on plasma KL-6.

Conclusions

KL-6 increases with ageing and chronic smoking history, but prospective studies will be needed to elucidate the significance of KL-6 in chronic airway diseases.