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.     

Urinary excretion of the acrylonitrile metabolite 2-cyanoethylmercapturic acid is correlated with a variety of biomarkers of tobacco smoke exposure and consumption

Acrylonitrile is an IARC class 2B carcinogen present in cigarette smoke. Urinary 2-cyanoethylmercapturic acid (CEMA) is an acrylonitrile metabolite and a potential biomarker for acrylonitrile exposure. The objective of this work was to study the dose response of CEMA in urine of non-smokers and smokers of different ISO tar yield cigarettes. We observed that smokers excreted >100-fold higher amounts of urinary CEMA than non-smokers. The CEMA levels in smokers were significantly correlated with ISO tar yield, daily cigarette consumption, and urinary biomarkers of smoke exposure. In conclusion, urinary CEMA is a suitable biomarker for assessing smoking-related exposure to acrylonitrile.     

The Neural Mechanisms Underlying the Acute Effect of Cigarette Smoking on Chronic Smokers

Although previous research had related structural changes and impaired cognition to chronic cigarette smoking, recent neuroimaging studies have associated nicotine, which is a main chemical substance in cigarettes, with improvements in cognitive functions (e.g. improved attention performance). However, information about the alterations of whole-brain functional connectivity after acute cigarette smoking is limited. In this study, 22 smokers underwent resting-state functional magnetic resonance imaging (rs-fMRI) after abstaining from smoking for 12 hours (state of abstinence, SOA). Subsequently, the smokers were allowed to smoke two cigarettes (state of satisfaction, SOS) before they underwent a second rs-fMRI. Twenty non-smokers were also recruited to undergo rs-fMRI. In addition, high-resolution 3D T1-weighted images were acquired using the same magnetic resonance imaging(fMRI)scanner for all participants. The results showed that smokers had structural changes in insula, thalamus, medial frontal cortex and several regions of the default mode network (DMN) compared with non-smokers. Voxel-wise group comparisons of newly developed global brain connectivity (GBC) showed that smokers in the SOA condition had higher GBC in the insula and superior frontal gyrus compared with non-smokers. However, smokers in the SOS condition demonstrated significantly lower GBC in several regions of the DMN, as compared with smokers in the SOA condition. These results suggest that structural integrity combined with dysfunction of the DMN might be involved in relapses after a short period of time among smokers.     

Delay discounting and probability discounting as related to cigarette smoking status in adults

This study examined relations between adult smokers and non-smokers and the devaluation of monetary rewards as a function of delay (delay discounting, DD) or probability (probability discounting, PD). The extent to which individuals discount value, either as a function of a reward being delayed or probabilistic, has been taken to reflect individual differences in impulsivity. Those who discount most are considered most impulsive. Previous research has shown that adult smokers discount the value of delayed rewards more than adult non-smokers. However, in the one published study that examined probability discounting in adult smokers and non-smokers, the smokers did not discount the value of probabilistic rewards more than the non-smoker controls. From this past research, it was hypothesized that measures of delay discounting would differentiate between smokers and non-smokers but that probability discounting would not. Participants were 54 (25 female) adult smokers (n = 25) and non-smokers (n = 29). The smokers all reported smoking at least 20 cigarettes per day, and the non-smokers reported having never smoked. The results indicated that the smokers discounted significantly more than the non-smokers by both delay and probability. Unlike past findings, these results suggest that both delay and probability discounting are related to adult cigarette smoking; however, it also was determined that DD was a significantly stronger predictor of smoking than PD.     

Factors contributing to chromosome damage in lymphocytes of cigarette smokers

Cigarette smoking is generally believed to be responsible for a substantial number of human health problems. However, the causal relationship between smoking, the induction of biological effects and the extent of health problems among smokers have not been fully documented. Using the recently developed lymphocyte micronucleus (MN) assay, we have evaluated the chromosome aberration frequencies in 67 cigarette smokers and 59 matched non-smoking control subjects. We found that the mean MN frequency (per 100 cells) in the smokers was slightly higher than that found in the non-smokers (0.71 +/- 0.23 and 0.58 +/- 0.05 respectively; p less than 0.08). Factors which contribute to the expression of chromosome aberrations were also investigated. A significant age-dependent increase in MN frequencies was observed in both groups (p less than 0.05). Linear regression analysis showed that the age-dependent effects among smokers (r = 0.54; p less than 0.02) was further enhanced by cigarette consumption (r = 0.62; p less than 0.005). Consumption of low potency 'one-a-day' type multivitamins had no effect on MN frequencies in either sex of non-smokers and in the 1 male smoker who took multivitamins but vitamin intake consistently reduced the MN frequencies among female smokers. Using a challenge assay, fidelity of DNA repair was evaluated. Lymphocytes from both smokers and non-smokers were irradiated with single doses of 0 or 100 cGy of X-rays or with double doses of 100 cGy of X-rays each separated by 15 or 60 min (100/15 or 100/60). Chromosome translocation frequencies were consistently higher after irradiation in lymphocytes from smokers than in those from non-smokers. Statistically significant differences were detected when the cells were irradiated with the double doses of 100 cGy X-rays each separated by 60 min (p less than 0.05). These data suggest that lymphocytes from smokers made more mistakes in the repair of DNA damage than cells from non-smokers. Our studies provide new insights into the genotoxic effects of cigarette smoke and new information which may be useful for understanding the mechanisms for induction of health problems from smoking.     

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 B₄, 20-hydroxy-leukotriene B₄, 20-carboxy-leukotriene B₄ 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 B₄ 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 B₄ 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 B₄, 20-carboxy-leukotriene B₄ and 3-chlorotyrosine were higher in smokers than in non-smokers; leukotriene B₄ and 20-carboxy-leukotriene B₄ 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 B₄ 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 B₄ and 3-chlorotyrosine. To conclude, leukotriene B₄ 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.     

Cigarette Smoking Causes Hearing Impairment among Bangladeshi Population

Lifestyle including smoking, noise exposure with MP3 player and drinking alcohol are considered as risk factors for affecting hearing synergistically. However, little is known about the association of cigarette smoking with hearing impairment among subjects who carry a lifestyle without using MP3 player and drinking alcohol. We showed here the influence of smoking on hearing among Bangladeshi subjects who maintain a lifestyle devoid of using MP3 player and drinking alcohol. A total of 184 subjects (smokers: 90; non-smokers: 94) were included considering their duration and frequency of smoking for conducting this study. The mean hearing thresholds of non-smoker subjects at 1, 4, 8 and 12 kHz frequencies were 5.63±2.10, 8.56±5.75, 21.06±11.06, 40.79±20.36 decibel (dB), respectively and that of the smokers were 7±3.8, 13.27±8.4, 30.66±12.50 and 56.88±21.58 dB, respectively. The hearing thresholds of the smokers at 4, 8 and 12 kHz frequencies were significantly (p<0.05) higher than those of the non-smokers, while no significant differences were observed at 1 kHz frequency. We also observed no significant difference in auditory thresholds among smoker subgroups based on smoking frequency. In contrast, subjects smoked for longer duration (>5 years) showed higher level of auditory threshold (62.16±19.87 dB) at 12 kHz frequency compared with that (41.52±19.21 dB) of the subjects smoked for 1-5 years and the difference in auditory thresholds was statistically significant (p<0.0002). In this study, the Brinkman Index (BI) of smokers was from 6 to 440 and the adjusted odds ratio showed a positive correlation between hearing loss and smoking when adjusted for age and body mass index (BMI). In addition, age, but not BMI, also played positive role on hearing impairment at all frequencies. Thus, these findings suggested that cigarette smoking affects hearing level at all the frequencies tested but most significantly at extra higher frequencies.     

Altered salivary profile in heavy smokers and its possible connection to oral cancer

Saliva is the first biological fluid to encounter inhaled cigarette smoke, whose numerous carcinogens and oxidants are responsible for the oral cancer so prevalent among smokers. Whole saliva, collected from 25 consenting heavy smokers and from a control group of 25 age- and gender-matched non-smokers, was subjected to sialochemical, biochemical, immunological and oxidative analyses. The mean flow rate was significantly higher in smokers than in non-smokers, as were the median activity value of superoxide dismutase (SOD) and the total salivary antioxidant capacity (ImAnOx) (by 32% and 12%, respectively, p=0.05). The salivary carbonyl concentration (an oxidative stress indicator) was significantly higher by 126% (p=0.0006) among smokers, while lactate dehydrogenase, albumin, total immunoglobulin G, and the metalloproteinases MMP-2 and MMP-9 concentrations were significantly lower in the smokers, by 86% (p=0.003), 65% (p=0.003), 61% (p=0.048), 35% (p=0.005) and 55% (p=0.035), respectively. Apparently, the oral cavity's salivary antioxidant system fails to cope with the severe attack of reactive oxygen species originating in cigarette smoke. Moreover, various other salivary functional and protective parameters also decreased among the smokers. Hence, further research aimed at examining the possibility of administration of agents as antioxidants or saliva substitutes to the oral cavity of smokers should be considered.     

A comparative study of the plasma level of arginase and rhodanese in smokers and non-smokers

The purpose of this investigation was to determine and compare the activities of arginase and rhodanese in the blood plasma of cigarette smokers and non-smokers.The activity of arginase in the blood plasma of smokers was higher than arginase activity in the non-smokers (NS), however,in the smokers with diseases (SWD), the increase was significant. The comparison between the activity of rhodanese in the SWD, smokers without diseases (SWOD) and NS blood plasma revealed a decrease in the activity of rhodanese in NS and no significant difference in the three groups with P=0.8677. This paper reported the enhancing effect of cigarette smoking could have on the disease state of smokers due to high arginase activity. Keywords; Rhodanese, Arginase, Cigarette smoking, Plasma.     

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.     

Cigarette Smoking and Platelet Aggregation

The influence of cigarette smoking on platelet aggregation was studied in habitual and non-habitual smokers. The results indicate that habitual smokers have a greater tendency to platelet aggregation than do non-habitual smokers. Acute effects of cigarette smoking were, however, not significant. The nucleotide content and the serotonin content of the platelets were analyzed. The adenosine nucleotide and serotonin contents were similar in smokers and non-smokers in the control state and neither showed significant changes on cigarette smoking. There were significant correlations between the control concentrations of the various nucleotides in both groups and there were even higher correlations after smoking. Platelet aggregation bore no demonstrable relationship to the nucleotide or serotonin contents of the platelet. We conclude that the long-term effect of smoking is probably more important than the acute effect.     

Lymphocytes,DNA adducts and genetic polymorphism for metabolic enzymes in low dose cigarette smokers

The aim of this study was to investigate the relationship between genetic polymorphism of metabolic enzymes and DNA adduct levels in lymphocytes of low dose cigarette smokers (less than 20 cigarettes per day). We previously reported the effects of cytochrome P4501A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) on lymphocyte DNA adducts. This time we considered not only CYP1A1 and GSTM1 but also cytochrome P4502E1 (CYP2E1) and glutathione S-transferase T1 (GSTT1). DNA adducts in lymphocytes obtained from low dose cigarette smokers (n = 41) and nonsmokers (n = 56) were measured by the 32P-postlabelling method. The adduct levels were compared regarding smoking status and polymorphic genotypes of these four enzymes. The mean SD of DNA adduct levels in all low dose cigarette smokers and non-smokers was 1 05 0 83 per 108 nucleotidesand 0 85 0 35 per 108 nucleotides, respectively. In low dose cigarette smokers, adduct levels were higher in the rare homozygous (MM) for CYP1A1-exon 7 polymorphism compared with the other types such as common homozygous (WW) and heterozygous (WM). CYP1A1-WM, MM in combination with GSTM1 null showed highest adduct levelamong low smokers. The low smokers with rare homozygous for CYP2E1 Dra1 polymorphism tended to have lower adduct levels than wild types. Low dose cigarette smokers with combined GSTM1 null and T1 null had a higher tendency for adduct levels than others. However none of the differences reached statistical significance.     

Sister-chromatid exchanges in lymphocytes of smokers in an experimental study

The frequency of sister-chromatid exchanges (SCEs) was studied in peripheral blood lymphocytes of 26 young male smokers and 10 non-smokers who had recently entered military service. The levels of SCEs were examined in 4 consecutive blood samples taken after short experimental periods of smoking only low-tar (LT) or medium-tar (MT) cigarettes. The incidence of SCEs was significantly higher in the the group of smokers than in the group of non-smokers. The SCE levels of the smokers were found to be associated with the personal smoking history; the observed increase in the SCE frequency correlated with the years of smoking measured as cumulative pack years. The difference in type of cigarette did not influence the SCE frequencies.     

Chromosome aberrations among cigarette smokers in Colombia

Worldwide, the annual morbimortality caused by cigarette smoking is a major public health concern. In Colombia, up to 33% of the adult population has smoked at some point in life, raising important national issues on the disease burden from tobacco. The aim of this study was to establish whether cigarette smoking increases the frequency of chromosome aberrations (CA) in peripheral blood lymphocytes of smokers (n = 52) compared with non-smokers (n = 52) in Popayán, Colombia. After signing a consent form, volunteers provided a blood sample (20 ml) to establish cell cultures at 52 h. For CA analysis, 100 complete metaphase cells from each subject were evaluated. The CA frequency was significantly higher in smokers (8.38 +/- 0.61) than in non-smokers (3.13 +/- 0.29), showing the highest number of CA (14.83 +/- 1.01) among heavy smokers (>20 pack-years). Interestingly, light smokers (< or =10 pack-years) also showed a significant increase in CA when compared to non-smokers (6.62 +/- 0.53 versus 3.13 +/- 0.29, P < 0.01, respectively). In addition, a significant positive correlation was found between the frequency of CA and the intensity of smoking in pack-years (R2 = 0.60). Our study indicates that the genotoxic effects in lymphocytes from smokers are most likely caused by cigarette smoke constituents, providing scientific evidence to encourage national campaigns to prevent tobacco consumption.     

Smoking Habits of Men Employed in Industry,and Mortality

A study of the relation between smoking habits and lung cancer in male industrial workers over a period of three years has confirmed the earlier findings in doctors that the death-rate from lung cancer correlates closely with the number of cigarettes smoked. Of 54,460 men studied 68.7% were current cigarette smokers. The annual mortality rate from lung cancer was 0.33 per thousand in non-smokers and ex-smokers, and 1.2 per thousand for all cigarette smokers, and higher in heavy smokers.Heavy cigarette smokers who retained the cigarette in the mouth between puffs (“drooping” cigarette habit) had an annual mortality rate of 4.1 per thousand.The mortality from coronary thrombosis in smokers was nearly three times that in non-smokers. A mortality gradient with rising consumption of cigarettes was observed.Some correlation between smoking and cancer of other sites and from non-neoplastic lung disease was observed in older men, but no correlation was found with other cardiovascular diseases and cerebrovascular diseases.     

Effect of opium smoking on concentrations of carcinoembryonic antigen and tissue polypeptide antigen

Previous studies have related opium and its pyrolysates to the risk of developing certain cancers. The aim of this work was to evaluate the clinical usefulness of determining carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) levels in habitual opium smokers. Serum CEA concentrations were measured in 128 opium smokers and in 44 controls of cigarette only smokers and 47 normal non-smokers by an EIA-based assay. TPA levels were also determined in serum and urine of a subgroup in the study population. The results indicated that serum CEA concentrations are higher in opium smokers than in healthy tobacco smokers (p = 0.004) and non-smokers (p = 0.001). The amount of opium used correlated with the serum CEA level (r = 0.276, p < 0.0001). The mean urine and serum TPA levels of the opium-addicted population were also higher than that of the non-smoking control group, but the differences were not statistically significant. We conclude that opium smoking is associated with elevated serum CEA levels. Therefore, for management of opium users with neoplastic diseases, increased levels of serum CEA should be viewed with caution to avoid misdiagnosis.     

Sister-chromatid exchange and cell proliferation in cultured lymphocytes of passively and actively smoking restaurant personnel

Sister-chromatid exchange frequencies were measured in peripheral lymphocytes of 12 cigarette smokers, 20 passive smokers, and 14 non-smokers with no regular exposure to tobacco smoke. All active and passive smokers worked as waiters and waitresses in restaurants. The passive smokers showed neither an increased mean SCE value nor an increased number of high SCE frequency cells (HFCs) when compared to non-exposed non-smokers. The incidence of SCEs and HFCs was observed to be elevated (P less than 0.01; P less than 0.05, resp.) among the active smokers. The proliferation rate of lymphocytes in whole blood cultures from the different exposure groups was also studied. The proportion of cells in first mitosis was lower and the mean replication index (RI) higher among the smokers than among non-smoker controls. However, no significant correlation was observed between the individual mean SCE and the replication index.     

Increased frequency of micronuclei in B and T8 lymphocytes from smokers

The frequency of micronuclei was measured in peripheral B lymphocytes and some T lymphocyte subpopulations from 5 medium-tar cigarette smokers, and 5 non-smokers with no regular exposure to tobacco smoke. The peripheral lymphocytes were stimulated in vitro with phytohemagglutinin and B lymphocytes and the various T lymphocyte subsets were classified by a recently developed MAC (Morphology, Antibody, Chromosomes) method which allows the immunologic identification of different cell lineages. An increased frequency of micronuclei was observed in B and especially in the suppressor/cytotoxic T8 lymphocytes from smokers, as compared with non-smoker values. In non-smoker cultures, no differences in the frequency of micronuclei were observed among the different T lymphocyte subsets. In these cultures, B cells tended to have a higher frequency of micronuclei than did T cells. The proportions of B cells and the various T subpopulations among mitotic and interphasic lymphocytes from smokers and non-smokers were also determined. The proportions of B cells and T cell subsets among all mitotic lymphocytes were similar in smokers and non-smokers. Contrarily, a significant decrease in the proportion of T8 lymphocytes among all interphasic lymphocytes was observed in cultures derived from smokers.     

Water-pipe smoking and metabolic syndrome: a population-based study

Water-pipe (WP) smoking has significantly increased in the last decade worldwide. Compelling evidence suggests that the toxicants in WP smoke are similar to that of cigarette smoke. The WP smoking in a single session could have acute harmful health effects even worse than cigarette smoking. However, there is no evidence as such on long term WP smoking and its impact on chronic health conditions particularly cardiovascular and metabolic conditions. Therefore, we conducted this study to investigate the relationship between WP smoking and metabolic syndrome (MetS). This was a cross-sectional study carried out in Punjab province of Pakistan using the baseline data of a population-based study - Urban Rural Chronic Diseases Study (URCDS). Information was collected by trained nurses regarding the socio-demographic profile, lifestyle factors including WP smoking, current and past illnesses. A blood sample was obtained for measurement of complete blood count, lipid profile and fasting glucose level. MetS was ascertained by using the International Diabetic Federation's criteria. We carried out multiple logistic regressions to investigate the association between WP smoking and MetS. Final sample included 2,032 individuals - of those 325 (16.0%) were current WP smokers. Age adjusted-prevalence of MetS was significantly higher among current WP smokers (33.1%) compared with non-smokers (14.8%). Water-pipe smokers were three times more likely to have MetS (OR 3.21, 95% CI 2.38-4.33) compared with non-smokers after adjustment for age, sex and social class. WP smokers were significantly more likely to have hypertriglyceridemia (OR 1.63, 95% CI 1.25-2.10), hyperglycaemia (OR 1.82, 95% CI 1.37-2.41), Hypertension (OR 1.95, 95% CI 1.51-2.51) and abdominal obesity (OR 1.93, 95% CI 1.52-2.45). However, there were no significant differences in HDL level between WP smokers and non-smokers. This study suggests that WP smoking has a significant positive (harmful) relationship with MetS and its components.     

Influence of Smoking on Deep Vein Thrombosis after Myocardial Infarction

As part of a study of the factors affecting the risk of deep vein thrombosis after myocardial infarction a surprising and unexplained finding was that non-smokers had a significantly higher incidence of thrombosis than cigarette smokers.