Association of 1 hydroxypyrene glucuronide in human urine with cigarette smoking and broiled or roasted meat consumption

Humans are exposed to polycyclic aromatic hydrocarbons PAHs from various occupational, dietary, environmental and medicinal sources. We measured 1 hydroxypyrene glucuronide 1 OHP gluc concentration in urines from male non smokers n = 50, smokers of blond tobacco n = 31, smokers of black tobacco n = 16, and pipe smokers n = 3 . Immunoaffinity chromatography was used as a preparative step and synchronous fluorescence spectroscopy as the quantitation method. The concentration of 1 OHP gluc in urine from smokers mean SE: 1.04 0.13 pmol ml-1 urine was significantly higher than in urine from non smokers 0.55 0.05 pmol ml-1 urine by the Wilcoxon rank sum test non smokers versus all smokers, p = 0.001; vs black tobacco smokers, p = 0.001; vs blond tobacco smokers, p = 0.007 . Urinary 1 OHP gluc concentration among subjects who had consumed roasted, grilled or broiled meat within the past 24 h was elevated compared with those who had not p = 0.025 . Multiple linear regression showed significant associations of urinary 1 OHP gluc with number of cigarettes smoked p = 0.002 and consumption of roasted, grilled or broiled meat p = 0.028 . Systemic CYP1A2 activity estimated by caffeine metabolism was significantly correlated with urinary 1 OHP gluc concentration. However, this association was probably due to cigarette smoking, since adjusting for cigarette smoking by multiple linear regression made the association between urinary 1 OHP gluc and CYP1A2 phenotype non significant. These results further support the use of urinary 1 OHP gluc as a biomarker of recent pyrene exposure through inhalation or diet.     

Use of Salmonella typhimurium TA 98, YG 1024 and YG 1021 and deconjugating enzymes for evaluating the mutagenicity from smokers'' urine

Four smokers were chosen for their different smoking habits, and their declared cigarette consumption confirmed by urinary measurement of nicotine and its metabolites. The promutagenicity of their urine was evaluated by the Ames test, modified according to Kado et al. (Mutation Res., 31 (1983) 25–32) after extraction on XAD2 Amberlite resin. The different Salmonella typhimurium strains TA 98, YG 1021 and YG 1024 were compared to determine the presence of amino aromatic compounds in the urine of smokers of blond and black tobacco. The strain YG 1024 shows higher mutagenicity than TA 98 for extracts from the smoker's urine and more particularly from black tobacco smokers. In addition, the pretreatment of urine by external enzymatic systems (β-glucuronidase or arylsulfatase) reveals the presence in the urine of glucurono- and sulfoconjugated forms of promutagens, including amino aromatic compounds.     

Mutagen levels in urine from snuff users, cigarette smokers and non tobacco users--a comparison

The mutagenic activity of concentrates of urine from snuff users, cigarette smokers and non tobacco users has been investigated. A concentration procedure involving use of Sep-Pak C18 columns and elution with methylene chloride was used. The concentrates were assayed for mutagenicity towards strain TA98 of Salmonella typhimurium, both in the presence and absence of a metabolic activation system, the post-mitochondrial liver fraction (S9) from Aroclor 1254 induced rats. The mean mutagenic activity of smokers' urine concentrates was 8.6 X 10(3) revertants per 24 h and significantly higher than the corresponding values for snuff users, abstinent snuff users and non tobacco users, which were (1.3, 1.3 and 0.9) X 10(3), respectively. No significant difference in mutagenic activity was found between urine from snuff users, whether using or abstaining from snuff, and urine from non tobacco users. It could thus be concluded that the level of urinary mutagens, isolated by adsorption on Sep-Pak C18 columns, is not elevated by habitual usage of Swedish wet snuff.     

Effects of lifestyle and genetic polymorphisms on consumption of coffee or black tea and urinary caffeine levels

To find the cause of individual differences in caffeine intake and its metabolism, we investigated the effects of lifestyle and genetic polymorphisms of caffeine metabolic enzymes on coffee or black tea and urinary caffeine levels among 259 male Japanese. It was seen that cigarette smokers drank more coffee or black tea than non-smokers (p < 0.001). There was an inverse correlation between the amount of coffee or black tea consumed and age or the frequency of alcohol drinking (p < 0.05). Genetic polymorphisms of N -acetyltransferase 2 (NAT2), cytochrome P450 (CYP)1A1 and 2E1 did not significantly affect the habit of drinking coffee or black tea. The frequency of allele 1, the NAT2 allele of rapid acetylators, increased according to coffee or black tea consumption (0.05 < p < 0.1). Among lifestyle factors, two factors, i.e. smoking and the amount of coffee or black tea consumed, were related to urinary caffeine levels (p < 0.05). Geometric means of urinary caffeine levels were higher in the group who consumed higher amounts of coffee or black tea (p < 0.05) and those of smokers were lower than non-smokers- approximately 70% of non-smokers (p < 0.05). The genetic polymorphisms of NAT2, CYP1A1 and CYP2E1 were not significantly associated with the urinary caffeine levels according to each consumption level of coffee or black tea. This study suggests that smoking should be considered for the proper appreciation of individual differences in caffeine intake and urinary caffeine levels.     

Influence of the genetic polymorphism in the 5'-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers

The functional significance of genetic polymorphisms on tobacco smoke-induced CYP1A2 activity was examined. The influence of three polymorphisms of the cytochrome P450 1A2 gene (CYP1A2) (-3860 G-->A (allele *1C), -2467 T-->delT (allele *1D), -163C-->A (allele *1F)), located in the 5'-noncoding promoter region of the gene, on CYP1A2 activity (measured as caffeine metabolic ratio, CMR), was studied in Caucasian current smokers (n=95). Tobacco smoke intake was calculated from the number of cigarettes/day. Also, studied was the influence of these CYP1A2 genotypes on smoking-associated urinary mutagenicity, detected in Salmonella typhimurium strain YG1024 with S9 mix, considering the urinary excretion of nicotine plus its metabolites as an internal indicator of tobacco smoke exposure. Smokers with at least one of the variant alleles CYP1A2 -3860A and -2467 delT showed a significantly increased CYP1A2 CMR (-3860 G/A versus G/G, p<0.05; -2467 delT/delT versus T/delT and T/T, p<0.01). Multiple regression analysis showed that the increase in CYP1A2 CMR (ln values) was again significantly related to the presence of CYP1A2 variants -2467delT and also to variant -163A (p<0.05), but moderately to -3860A (p=0.084). No influence of the number of cigarettes smoked per day by each subject was found. Heavy smokers (n=48, with urinary nicotine plus its metabolites>or=0.69 mg/mmol creatinine) with variant allele -2467delT or -163A had significantly increased urinary mutagenicity (p<0.01 and <0.05). CYP1A2 genetic polymorphisms are shown to influence the CYP1A2 phenotype in smokers, -2467 T-->delT having the main effect. This information is of interest for future studies assessing the possible role of tobacco smoke-inducible CYP1A2 genotypes as individual susceptibility factors in exposure to carcinogens.     

Determination of tobacco-specific N-nitrosamines in urine of smokers and non-smokers

Tobacco-specific N-nitrosamines (TSNA) include 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N′-nitrosonornicotine (NNN), N′-nitrosoanabasine (NAB) and N′-nitrosoanatabine (NAT) and are found in tobacco and tobacco smoke. TSNA are of interest for biomonitoring of tobacco-smoke exposure as they are associated with carcinogenesis. Both NNK and NNN are classified by IARC as Group 1 carcinogens. Samples of 24?h urine collections (n?=?108) were analysed from smokers and non-smokers, using a newly developed and validated LC-MS/MS method for determining total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the major metabolite of NNK), and total NNN, NAB and NAT. TSNA levels in smokers’ urine were significantly higher than in non-smokers. In smokers, urinary excretion of total TSNA correlated significantly (r?>?0.5) with markers of smoking dose, such as daily cigarette consumption, salivary cotinine and urinary nicotine equivalents and increased with the ISO tar yield of cigarettes smoked. The correlation between urinary total NNN and the smoking dose was weaker (r?=?0.4–0.5). In conclusion, this new method is suitable for assessing tobacco use-related exposure to NNK, NNN, NAB and NAT.     

The effect of exposure to nicotine, carbon monoxide, cigarette smoke or cigarette smoke condensate on the mutagenicity of rat urine

Cigarette smokers have been reported to void urine which is more mutagenic than that voided by non-smokers, but the specific urinary mutagen(s) have not been identified. Since mechanistic studies are best performed in animal models, the objective of this study was to determine if a model to study the role of cigarette smoke and its components in urinary mutagenicity could be developed in rats. XAD-2 resin was used to concentrate the urine and the microsuspension modification of the Ames test used to quantify mutagenicity. Nicotine administered by intraperitoneal injection at 0.8 mg/kg (the maximum tolerated dose) or inhalation of carbon monoxide for 14 days at the maximum tolerated dose (1800 ppm, resulting in 68% carboxyhemoglobin) did not increase urinary mutagenicity. Cigarette smoke condensate (CSC) prepared by electrostatic precipitation of mainstream smoke increased urinary mutagenicity at doses of 100 and 200 mg/kg when administered acutely by either i.p. injection or gavage, verifying that the assay system was capable of detecting cigarette smoke-related mutagens in the urine. However, cigarette smoke administered by the appropriate route of exposure, nose-only inhalation, for 1, 7, 14 or 90 days (1 h per day) did not increase urinary mutagenicity. The smoke concentration administered was at or near the maximum tolerated dose as evidenced by carboxyhemoglobin concentrations of approximately 50%, and of 10% or more weight loss in exposed animals. Thus, although cigarette smoke condensate is mutagenic in vitro and mutagenic urine was observed when rats were given high doses of CSC by inappropriate routes of administration, acute or subchronic inhalation exposure to the maximum tolerated dose of whole cigarette smoke did not increase urinary mutagenicity in rats. These results indicate that the rat may be an inappropriate model to study urinary mutagenicity following the inhalation of tobacco smoke.     

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.     

Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in smokers in the united states: NHANES 2007–2008

The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), has been measured in urine samples from all participants aged 6 years and older from the National Health and Nutrition Examination Survey 2007–2008. Participants with a serum cotinine concentration of ≥10?ng/mL were identified as tobacco users, primarily cigarette smokers. Regression models were developed to calculate geometric mean NNAL concentrations adjusted for serum cotinine, urinary creatinine, cigarettes per day, and Federal Trade Commission tar values of the cigarettes smoked. Significant differences were found by gender (p?=?0.003) and race/ethnicity (p?=?0.022 for non-Hispanic white versus non-Hispanic black smokers), but not by menthol type of the cigarettes. Females and non-Hispanic white smokers had the highest adjusted means for urinary NNAL (353 and 336 pg/mL, respectively). The results from this study demonstrated significant relationships between NNAL concentrations and serum cotinine (p?<?0.001) and urine creatinine (p?<?0.001). The joint effect of linear and quadratic terms for number of cigarettes smoked per day was also statistically significant (p?=?0.001). In addition to addressing current NNK exposure levels, these results will form a baseline for future estimates of tobacco users’ exposure to this carcinogen.     

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.     

A cross-sectional survey of cadmium biomarkers and cigarette smoking

Cadmium contamination of tobacco may contribute to the health hazards of cigarette smoking. The 2005–2012 United States National Health and Nutrition Examination Survey data provided a unique opportunity to conduct a cross-sectional survey of cadmium biomarkers and cigarette smoking. Among a sample of 6761 participants, we evaluated mean differences and correlations between cadmium biomarkers in the blood and urine and characteristics of never, former and current smokers. We found statistically significant differences in mean cadmium biomarker levels between never and former smokers as well as between never and current smokers. In current smokers, duration in years had a higher correlation coefficient with urinary than blood cadmium levels. In contrast, number of cigarettes smoked per day had a higher correlation coefficient with blood than urinary cadmium levels. These data suggest that blood and urine cadmium biomarker levels differ by duration and dose. These findings should be considered in evaluating any association between cadmium and smoking related diseases, especially cardiovascular disease.     

Determination of urinary and salivary cotinine using gas and liquid chromatography and enzyme-linked immunosorbent assay

The objective of this study was to compare cotinine concentrations in urine and saliva using gas chromatography (GC), high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA). Ninety-four subjects were selected (27 smokers and 67 non-smokers) and interviewed using questionnaire. Of the non-smokers, 39 had been exposed to environmental tobacco smoke (ETS) and 28 had not been exposed to ETS. Cotinine levels among smokers were highest using all three measurements, followed by ETS exposed subjects and non-smokers. Cotinine levels in urine, using HPLC, correlated significantly with levels measured using ELISA (r=0.92) and GC-nitrogen-phosphorus detection (NPD) (r=0.92). Salivary cotinine levels measured using ELISA did not correlate significantly with either HPLC (r=0.37) or GC-NPD (r=0.33) measurements. Multiple regression models were used to adjust for age, gender, drug use and health status, and it was found that cotinine levels in urine and saliva were significantly correlated with smoking pack-year. The authors conclude that urinary cotinine concentration is a more accurate biomarker for ETS than salivary cotinine concentration.     

Oxidative DNA damage in vivo: relationship to age, plasma antioxidants, drug metabolism, glutathione-S-transferase activity and urinary creatinine excretion

Oxidative DNA modification has been implicated in development of certain cancers and 8-oxodG, the most abundant and mutagenic DNA modification, has for some time been considered a biomarker of this activity. Urinary excretion of 8-oxodG over 24h has been used to estimate the rate of damage to DNA, and animal studies have supported this rationale. Reported determinants include tobacco smoking, heavy exercise, environmental pollution and individual oxygen consumption. Samples from three published studies were used to determine the association of urinary 8-oxodG excretion with age, plasma antioxidants, the glutathione-S-transferase phenotype and the activity of the xenobiotic metabolising enzyme CYP1A2. In the age range 35-65 years, age was not related to urinary 8-oxodG excretion, and there were no relations to either the glutathione-S-transferase phenotype or to the plasma antioxidants: vitamin C, alpha-tocopherol, beta-carotene, lycopene or coenzyme Q10. The activity of CYP1A2 showed a significant correlation in two of the three studies, as well as a significant correlation of 0.26 (p < 0.05) in the pooled data set. Regression analysis of CYP1A2 activity on 8-oxodG indicated that 33% increase in CYP1A2 activity would correspond to a doubling of 8-oxodG excretion. This finding needs to be confirmed in independent experiments. Spot morning urine samples can under certain circumstances be used to estimate 8-oxodG excretion rate provided that creatinine excretion is unchanged (in paired experiments) or comparable (in un-paired experiments), as evaluated from the correlation between 8-oxodG excretion in 24 h urine samples and in morning spot urine samples corrected for creatinine excretion (r = 0.50, p < 0.05). We conclude that 8-oxodG excretion is determined by factors like oxygen consumption and CYP1A2 activity rather than by factors like plasma antioxidant concentrations.     

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.     

Biomonitoring of environmental tobacco smoke (ETS)-related exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

The exposure of non-smokers to the tobacco-specific N-nitrosamine 4-(N-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a rodent lung carcinogen, was determined in the air of various indoor environments as well as by biomonitoring of non-smokers exposed to environmental tobacco smoke (ETS) under real-life conditions using the urinary NNK metabolites 4-(N-methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and [4-(N-methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc). NNK was not detectable (&lt;0.5 ng m^-3) in 11 rooms in which smoking did not occur. The mean NNK concentration in 19 rooms in which smoking took place was 17.5 (2.4-50.0) ng m^-3. The NNK levels significantly correlated with the nicotine levels (r=0.856; p&lt; 0.0001). Of the 29 non-smokers investigated, 12 exhibited no detectable NNAL and NNAL-Gluc excretion (&lt;3 pmol day) in their urine. The mean urinary excretion of NNAL and NNAL-Gluc of the 17 remaining non-smokers was 20.3 (&lt;3-63.2) and 22.9 (&lt;3-90.0) pmol day^-1, respectively. Total NNAL excretion (NNAL+NNAL-Gluc) in all non-smokers investigated significantly correlated with the amount of nicotine on personal samplers worn during the week prior to urine collection (r=0.88; &lt;0.0001) and with the urinary cotinine levels (r=0.40; p=0.038). No correlation was found between NNAL excretion and the reported extent of ETS exposure. Average total NNAL excretion in the non-smokers with detectable NNAL levels was 74 times less than in 20 smokers who were also investigated. The cotinine/total NNAL ratios in urine of smokers (9900) and non-smokers (9300) were similar. This appears to be at variance with the ratios of the corresponding precursors (nicotine/NNK) in mainstream smoke (16400) and ETS (1000). Possible reasons for this discrepancy are discussed. The possible role of NNK as a lung carcinogen in non-smokers is unclear, especially since NNK exposure in non-smokers is several orders of magnitude lower than the ordinary exposure to exogenous and endogenous N-nitrosamines and the role of NNK as a human lung carcinogen is not fully understood.     

Cigarette smokers have decreased lymphocyte and platelet alpha-tocopherol levels and increased excretion of the gamma-tocopherol metabolite gamma-carboxyethyl-hydroxychroman (gamma-CEHC)

Cigarette smoking is associated with increased oxidative stress and increased risk of degenerative disease. As the major lipophilic antioxidant, requirements for vitamin E may be higher in smokers due to increased utilisation. In this observational study we have compared vitamin E status in smokers and non-smokers using a holistic approach by measuring plasma, erythrocyte, lymphocyte and platelet alpha- and gamma-tocopherol, as well as the specific urinary vitamin E metabolites alpha- and gamma-carboxyethyl-hydroxychroman (CEHC). Fifteen smokers (average age 27 years, smoking time 7.5 years) and non-smokers of comparable age, gender and body mass index (BMI) were recruited. Subjects completed a 7-day food diary and on the final day they provided a 24 h urine collection and a 20 ml blood sample for measurement of urinary vitamin E metabolites and total vitamin E in blood components, respectively. No significant differences were found between plasma and erythrocyte alpha- and gamma-tocopherol in smokers and non-smokers. However, smokers had significantly lower alpha-tocopherol (mean+/-SD, 1.34+/-0.31 micromol/g protein compared with 1.94+/-0.54, P = 0.001) and gamma-tocopherol (0.19+/-0.04 micromol/g protein compared with 0.26+/-0.08, P = 0.026) levels in their lymphocytes, as well as significantly lower alpha-tocopherol levels in platelets (1.09+/-0.49 micromol/g protein compared with 1.60+/-0.55, P = 0.014; gamma-tocopherol levels were similar). Interestingly smokers also had significantly higher excretion of the urinary gamma-tocopherol metabolite, gamma-CEHC (0.49+/-0.25mg/g creatinine compared with 0.32+/-0.16, P = 0.036) compared to non-smokers, while their alpha-CEHC (metabolite of alpha-tocopherol) levels were similar. There was no significant difference between plasma ascorbate, urate and F2-isoprostane levels. Therefore in this population of cigarette smokers (mean age 27 years, mean smoking duration 7.5 years), alterations to vitamin E status can be observed even without the more characteristic changes to ascorbate and F2-isoprostanes. We suggest that the measurement of lymphocyte and platelet vitamin E may represent a valuable biomarker of vitamin E status in relation to oxidative stress conditions.     

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.     

Estimation of urinary cotinine cut-off points distinguishing non-smokers,passive and active smokers

Abstract

An objective assessment of exposure to tobacco smoke may be accomplished by means of examining particular biomarkers in body fluids. The most common biomarker of tobacco smoke exposure is urinary, or serum, cotinine. In order to distinguish non-smokers from passive smokers and passive smokers from active smokers, it is necessary to estimate cotinine cut-off points. The objective of this article was to apply statistical distribution of urinary cotinine concentration to estimate cut-off points distinguishing the three above-mentioned groups. The examined group consisted of 327 volunteers (187 women and 140 men) who were ethnically homogenous inhabitants of the same urban agglomeration (Sosnowiec, Poland). The values which enabled differentiation of the examined population into groups and subgroups were as follows: 50 µg l^?1 (differentiation of non-smokers from passive smokers), 170 µg l^?1 (to divide the group of passive smokers into two subgroups: minimally and highly exposed to environmental tobacco smoke), 550 µg l^?1 (differentiation of passive smokers from active smokers), and 2100 µg l^?1 (to divide group of active smokers into two subgroups: minimally and highly exposed to tobacco smoke). The results suggest that statistical distribution of urinary cotinine concentration is useful for estimating urinary cotinine cut-off points and for assessing the smoking status of persons exposed to tobacco smoke.     

Cigarette smoking may reduce plasma leptin concentration via catecholamines

BACKGROUND: Leptin might influence body weight among smokers. DESIGN: (A) Screening of plasma leptin levels in 222 sedentary, smoking and non-smoking middle-aged men. (B) Double-blind, placebo-controlled smoking intervention on smokers (n=31). (C) Non-smokers (n=40) received chewing gum with nicotine (2mg nicotine, n=23) or without nicotine (n=19). (D) The effects of nicotine (0.05 and 0.5 microg/mL) were monitored on leptin secretion and mRNA levels in a human placental cell line (BeWo) expressing leptin, a murine adipocyte cell line (3T3-L1) and human adipose tissue explants. RESULTS: (A) Plasma leptin levels in smoking men (8.4+/-8.4 ng/mL, n=100) was lower as compared to non-smokers (10.3+/-7.3 ng/mL, n=122) (P<0.001), even when adjusted for differences in body mass index (BMI) (P<0.001). (B) A significant reduction (P=0.02) in plasma concentration of leptin was found already after smoking one cigarette. Concomitant with the 3-5 fold increase in plasma nicotine concentration after the first cigarette, we observed increased plasma adrenaline levels (P=0.005). (C) There was no effect of nicotine on plasma leptin levels in non-smokers receiving nicotine-containing chewing gum, and plasma concentrations of catecholamines were unaltered. (D) There was no effect of nicotine on leptin mRNA expression after incubation with cells or adipose tissue. CONCLUSION: Cigarette smoking reduced plasma leptin concentration in vivo, whereas nicotine had no direct effect on leptin expression in vitro. Nicotine might indirectly reduce leptin secretion via enhanced plasma catecholamine concentration.     

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.