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Biomedical subjects

Stephen S Hecht

Publications and source records attributed to Stephen S Hecht.

At least 19 recordsLinked to original sources
PubMed2007

Quantitation of an acetaldehyde adduct in human leukocyte DNA and the effect of smoking cessation.

Acetaldehyde is one of the most prevalent carcinogens in cigarette smoke. It is also a major metabolite of ethanol and is found widely in the human diet and environment. Acetaldehyde DNA adducts are critical for its carcinogenic properties. The role of acetaldehyde DNA adducts in human cancer related to tobacco and alcohol exposure could be investigated with a suitable biomarker. Therefore, in this study, we have developed a method for analysis of the major DNA adduct of acetaldehyde, N2-ethylidene-dGuo (1), in human leukocyte DNA. Leukocyte DNA was subjected to enzyme hydrolysis in the presence of NaBH3CN, which converts adduct 1 to N2-ethyl-dGuo (2). [15N5]N2-ethyl-dGuo was used as the internal standard. After solid-phase extraction, N2-ethyl-dGuo was quantified by LC-ESI-MS/MS-SRM. The method was sensitive, accurate, and precise, and applicable to low microgram amounts of DNA. It was applied to investigate the effect of smoking cessation on levels of adduct 1, measured as adduct 2. Twenty-five smokers who were only light drinkers were eligible for the study. Levels of adduct 2 were quantified at two baseline time points separated by one week and again after four weeks of abstinence from smoking and alcohol consumption. The mean (+/-S.D.) levels of adduct 2 measured in the leukocytes of the smokers were 1310 +/- 1720 (range 124-7700) and 1120 +/- 1140 (range 138-5760) fmol/micromol dGuo at the two baseline points and 705 +/- 438 (range 111-1530) fmol/micromol dGuo after 4 weeks of cessation. The median level of adduct 2 decreased significantly by 28% upon quitting smoking (P = 0.02). These results demonstrate that the major acetaldehyde DNA adduct can be reliably quantified by MS/MS methods in human leukocyte DNA and that cigarette smoking has a modest but significant effect on its levels.

Acetaldehyde↗
PubMed2006

Replication-coupled repair of crotonaldehyde/acetaldehyde-induced guanine-guanine interstrand cross-links and their mutagenicity.

The repair of acetaldehyde/crotonaldehyde-induced guanine (N2)-guanine (N2) interstrand cross-links (ICLs), 3-(2-deoxyribos-1-yl)-5,6,7,8-(N2-deoxyguanosyl)-6(R or S)-methylpyrimido[1,2-alpha]purine-10(3H)-one, was studied using a shuttle plasmid bearing a site-specific ICL. Since the authentic ICLs can revert to monoadducts, a chemically stable model ICL, 1,3-bis(2'-deoxyguanos-N2-yl)butane derivative, was also employed to probe the ICL repair mechanism. Since the removal of ICL depends on the nucleotide excision repair (NER) mechanism in Escherichia coli, the plasmid bearing the model ICL failed to yield transformants in NER-deficient host cells, proving the stability of this ICL in cells. The authentic ICLs yielded transformants in the NER-deficient hosts; therefore, these transformants are produced by plasmid bearing spontaneously reverted monoadducts. In contrast, in NER-deficient human cells, the model ICL was removed by an NER-independent repair pathway, which is unique to higher eukaryotes. This repair did not associate with a transcriptional event, but with replication. The analysis of repaired molecules revealed that the authentic and model ICLs were repaired mostly (>94%) in an error-free manner in both hosts. The major mutations that were observed were G --> T transversions targeting the cross-linked dG located in the lagging strand template. These results support one of the current models for the mammalian NER-independent ICL repair mechanism, in which a DNA endonuclease(s) unhooks an ICL from the leading strand template at a stalled replication fork site by incising on both sides of the ICL and then translesion synthesis is conducted across the "half-excised" ICL attached to the lagging strand template to restore DNA synthesis.

Acetaldehyde↗
PubMed2006

Cigarette smoking: cancer risks, carcinogens, and mechanisms.

BACKGROUND: Cigarette smoking causes about 30% of all cancer mortality in developed countries. Although smoking is decreasing in developed countries, it is increasing in some developing countries. DISCUSSION: Cigarette smoke contains over 60 well established carcinogens. There are strong links between some of these carcinogens and various types of smoking-induced cancers. Mechanisms by which cigarette smoke carcinogens cause cancer are well established and are discussed here. CONCLUSIONS: A great deal is known about cigarette smoke carcinogens and the mechanisms by which they cause cancer. It is hoped that this will provide new insights for the prevention and cure of tobacco-induced cancer.

Carcinogens↗
PubMed2006

A biomarker of exposure to environmental tobacco smoke (ETS) and Ernst Wynder's opinion about ETS and lung cancer.

Ernst Wynder did not believe that environmental tobacco smoke (ETS), also known as secondhand smoke, was a cause of lung cancer because his own data did not support this. His view on the issue may have begun to change with our initial studies, carried out at the American Health Foundation, showing that metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were present in the urine of non-smokers exposed to ETS. The metabolites - 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs) - have now emerged as leading biomarkers for the study of carcinogen exposure in non-smokers exposed to ETS. Subsequent work has consistently demonstrated elevated levels of NNAL plus NNAL-Glucs in the urine of people exposed to ETS in various field studies and throughout life. These studies strongly support the epidemiologic data demonstrating that ETS exposure causes lung cancer in non-smokers and have likely had an impact on tobacco control.

Air Pollution, Indoor↗
PubMed2006

Genotoxicity of acetaldehyde- and crotonaldehyde-induced 1,N2-propanodeoxyguanosine DNA adducts in human cells.

Reaction of crotonaldehyde or two molecules of acetaldehyde with DNA generates 3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2-a]purine-10(3H)one (2, Scheme 1), which occurs in (6R, 8R) and (6S, 8S) configurations (Fig. 1). These diastereomers were site-specifically incorporated into oligonucleotides, which were then inserted into a double-stranded DNA vector for genotoxicity studies. Modified DNA was introduced into human xeroderma pigmentosum A (XPA) cells to allow replication. Analysis of progeny plasmid revealed that these DNA adducts inhibit DNA synthesis to similar degrees. (6S, 8S)-2 miscodes more frequently than (6R, 8R)-2: 10% versus 5%. For both adducts, major miscoding events were G-->T transversions, but G-->A transitions were also observed at a comparable level for (6R, 8R)-2. G-->C transversions were the second most common events for (6S, 8S)-2. Comparison of these results with those of other 1,N2-propanodeoxyguanosine (PdG) adducts, which were evaluated by the same system, indicates that (i) their synthesis inhibiting potencies are stronger than that of the unsubstituted analog, 3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10(3H)one (1, Scheme 1), but weaker than that of 3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-6-hydroxypyrimido[1,2-a]purine-10(3H)one (3, Scheme 1); (ii) both isomers of 2 are more miscoding than 1; (iii) the miscoding potency of (6S, 8S)-2 is comparable to those of 3 and a model PdG 4 lacking a hydroxyl and a methyl group (Fig. 1). Therefore, considering the fact that 2 are formed endogenously as well as exogenously, they may play a significant role in aging and cancer in humans.

Acetaldehyde↗
PubMed2006

Identification of cyanidin glycosides as constituents of freeze-dried black raspberries which inhibit anti-benzo[a]pyrene-7,8-diol-9,10-epoxide induced NFkappaB and AP-1 activity.

Dietary freeze-dried black raspberries inhibit tumor induction by N-nitrosomethylbenzylamine in the rat esophagus, but the constituents responsible for this chemopreventive activity have not been identified. We fractionated freeze-dried black raspberries and used mouse epidermal JB6 Cl 41 cells stably transfected with either a nuclear factor kappa B (NFkappaB)- or an activator protein 1 (AP-1)-luciferase reporter, and treated with racemic anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), to assess the inhibitory effects of the fractions. The ethanol and water extracts of the freeze-dried black raspberries had inhibitory activity and these extracts were fractionated by HPLC to give several bioactive fractions. Further HPLC analysis yielded multiple subfractions, some of which inhibited BPDE-induced NFkappaB activity. Major constituents of the most active subfractions were identified by their spectral properties and in comparison with standards as cyanidin-3-O-glucoside, cyanidin 3-O-(2(G)-xylosylrutinoside) and cyanidin 3-O-rutinoside. Analysis of freeze-dried black raspberries indicated that these three components comprised approximately 3.4% of the material by dry weight. Consistent with these results, standard cyanidin-3-O-glucoside and cyanidin chloride were also good inhibitors of BPDE-induced NFkappaB activity. The results of this study demonstrate that cyanidin glycosides of freeze-dried black raspberries are bioactive compounds which could account for at least some of the chemopreventive activity observed in animal models.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2006

Oral creatine supplementation in humans does not elevate urinary excretion of the carcinogen N-nitrososarcosine.

OBJECTIVE: Creatine is a popular oral supplement in athletes and may have therapeutical potential in neuromuscular diseases. It has been hypothesized that creatine ingestion can lead to increased formation of the carcinogen N-nitrososarcosine. METHODS: We investigated in a double-blind, placebo-controlled study the urinary excretion of N-nitrososarcosine after 1-wk high-dose (20 g/d) and 20-wk low-dose (5 g/d) creatine supplementation in healthy humans. RESULTS AND CONCLUSION: Creatine ingestion does not systematically increase urinary N-nitrososarcosine excretion.

Administration, Oral↗
PubMed2006

Identification of an acetaldehyde adduct in human liver DNA and quantitation as N2-ethyldeoxyguanosine.

Acetaldehyde, an ubiquitous mutagen and carcinogen, could be involved in human cancer etiology. Because DNA adducts are important in carcinogenesis, we have used liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) to explore the presence in human liver DNA of the major acetaldehyde DNA adduct, N2-ethylidenedeoxyguanosine (1). DNA was isolated and enzymatically hydrolyzed in the presence of NaBH3CN, which quantitatively converts adduct 1 to N2-ethyldeoxyguanosine (N2-ethyl-dGuo, 2). [15N5]N2-Ethyl-dGuo was synthesized and used as an internal standard. Adduct 2 was enriched from the hydrolysate by solid phase extraction and analyzed by LC-ESI-MS/MS. Clear peaks were observed for adduct 2 in analyses of human liver DNA, calf thymus DNA, and rat liver DNA. These peaks were not observed, or were much smaller, when the NaBH3CN step was omitted. When the DNA was subjected to neutral thermal hydrolysis prior to NaBH3CN treatment, adduct 2 was not observed. Control experiments using [13C2]acetaldehyde demonstrated that adducts 1 and 2 were not formed as artifacts during DNA isolation and analysis. These results strongly indicate that adduct 1 is present in human liver DNA and demonstrate that it can be quantified as adduct 2. Levels of adduct 2 measured in 12 human liver samples were 534 +/- 245 fmol/micromol dGuo (mean +/- SD). The results of this study establish the presence of an acetaldehyde adduct in human liver DNA and suggest that it is a commonly occurring endogenous DNA adduct.

Acetaldehyde↗
PubMed2006

Identification of adducts formed in the reaction of 5'-acetoxy-N'-nitrosonornicotine with deoxyguanosine and DNA.

N'-Nitrosonornicotine (NNN) is believed to play an important role as a cause of cancer in people who use tobacco products and is considered to be a human carcinogen. NNN requires metabolism to form DNA adducts, which are absolutely critical to its carcinogenic properties. Previous studies have identified cytochrome P450-catalyzed 2'- and 5'-hydroxylation of NNN as potential DNA adduct forming metabolic pathways. 5'-Hydroxylation is the more prevalent of these in monkeys and humans and is known to generate mutagenic intermediates, but the DNA adducts formed by this pathway have never been characterized. In this study, we used 5'-acetoxyNNN as a stable precursor to 5'-hydroxyNNN and investigated its esterase-catalyzed reactions with deoxyguanosine (dGuo) and DNA. Adducts resulting from carbocation and oxonium ion intermediates, produced by the spontaneous decomposition of 5'-hydroxyNNN, were identified. The carbocation pathway resulted in the formation of 2-[2-hydroxy-5-(3-pyridyl)pyrrolidin-1-yl]deoxyinosine (12) which was characterized by comparison to an independently synthesized standard. Treatment of 12 with NaBH(3)CN produced two diastereomers of 2-[2-(3-pyridyl)pyrrolidin-1-yl]deoxyinosine (14), and their absolute configurations at the 2-position were determined by comparison to synthetic standards. The oxonium ion pathway produced diastereomers of N(2)[5-(3-pyridyl)tetrahydrofuran-2-yl]dGuo (16), identified by comparison to synthetic standards. The absolute configuration at the 5-position was determined by establishing the stereochemistry of the enantiomers of 5-(3-pyridyl)-2-hydroxytetrahydrofuran at the 5-position and allowing these to react individually with dGuo. Treatment of 16 with NaBH(3)CN produced N(2)[4-hydroxy-4-(3-pyridyl)but-1-yl]dGuo (18) which was also synthesized independently. Using liquid chromatography-electrospray ionization-tandem mass spectrometry with selected reaction monitoring, we identified adducts 12 and 16 as products of the reactions of 5'-acetoxyNNN with dGuo. Similarly, adducts 14 and 18 were identified as products of the reaction of 5'-acetoxyNNN with DNA followed by NaBH(3)CN treatment and enzymatic hydrolysis. These results provide the first structural characterization of DNA adducts that can be formed by 5'-hydroxylation of NNN.

Chromatography, High Pressure Liquid↗
PubMed2006

Quantitation of pyridyloxobutyl DNA adducts of tobacco-specific nitrosamines in rat tissue DNA by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

The tobacco-specific nitrosamines N'-nitrosonornicotine (NNN, 1) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 2) are potent carcinogens in rodents. Bioactivation of NNN and NNK by cytochrome P450 enzymes generates a pyridyloxobutylating agent 6, which alkylates DNA to produce pyridyloxobutyl (POB)-DNA adducts. POB-DNA adduct formation plays a critical role in NNN and NNK carcinogenicity in rodents. To further investigate the significance of this pathway, we developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method for quantitative analysis of four POB-DNA adducts with known structures. The corresponding deuterated analogues were synthesized and used as internal standards. DNA samples, spiked with internal standards, were subjected to neutral thermal hydrolysis followed by enzymatic hydrolysis. The hydrolysates were partially purified by solid phase extraction prior to HPLC-ESI-MS/MS analysis. The method was accurate and precise. Excellent sensitivity was achieved, especially for O2-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine (O2-POB-dThd, 11) with a detection limit of 100 amol per mg DNA. DNA samples treated with different concentrations of 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc, 3) were subjected to HPLC-ESI-MS/MS analysis. 7-[4-(3-Pyridyl)-4-oxobut-1-yl]guanine (7-POB-Gua, 12) was the most abundant adduct, followed by O6-[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxyguanosine (O6-POB-dGuo, 8), O2-POB-dThd, and O2-[4-(3-pyridyl)-4-oxobut-1-yl]cytosine (O2-POB-Cyt, 13). Lung and liver DNA isolated from NNK-treated rats were analyzed. Consistent with the in vitro data, 7-POB-Gua was the major POB-DNA adduct formed in vivo. However, levels of O6-POB-dGuo were the lowest of the four adducts analyzed, suggesting efficient repair of this adduct in vivo. In contrast to the other three adducts, O6-POB-dGuo was more abundant in lung than in liver. O2-POB-dThd appeared to be poorly repaired in vivo, and its levels were comparable to those of 7-POB-Gua. The results of this study provide a sensitive HPLC-ESI-MS/MS method for comprehensive quantitation of four POB-DNA adducts, support an important role of O6-POB-dGuo in NNK lung tumorigenicity in rats, and suggest that O2-POB-dThd may be a useful tobacco-specific DNA biomarker for future tobacco carcinogenesis studies.

Animals↗
PubMed2006

Quantitation of N-acetyl-S-(9,10-dihydro-9-hydroxy-10-phenanthryl)-L-cysteine in human urine: comparison with glutathione-S-transferase genotypes in smokers.

There are major interindividual differences in carcinogenic polycyclic aromatic hydrocarbon (PAH) metabolism in humans, and it has been hypothesized that these differences may be related to cancer risk in smokers and other exposed people. One important pathway of PAH metabolism involves the detoxification of the epoxide and diol epoxide metabolites by reaction with glutathione, catalyzed by glutathione-S-transferases (GSTs). Interindividual differences in these pathways have been examined by genotyping methods, investigating polymorphisms in GSTM1 and GSTP1. We are developing a phenotyping approach to assessing individual differences in PAH metabolism by quantifying human urinary metabolites of the ubiquitous PAH phenanthrene (1). In this study, we developed a method for quantitation of a mercapturic acid, N-acetyl-S-(9,10-dihydro-9-hydroxy-10-phenanthryl)-l-cysteine (PheO-NAC, 12), the end product of the reaction of phenanthrene-9,10-epoxide (11) with glutathione. [D(10)]PheO-NAC was added to the urine as internal standard, and the PheO-NAC fraction was enriched by solid-phase extraction. PheO-NAC was quantified by liquid chromatography electrospray ionization tandem mass spectrometry with selected reaction monitoring. The detection limit was approximately 4 fmol/mL of urine. PheO-NAC was detected in the urine of 46 of 104 smokers, mean (S.D.) 57.9 +/- 144 fmol/mL. PheO-NAC was detected significantly more frequently (P < 0.0001) in subjects who were GSTM1 positive than in those who were GSTM1 null, and the levels of PheO-NAC were significantly higher in the GSTM1 positive subjects, consistent with a role for GSTM1 in the detoxification of phenanthrene-9,10-epoxide. There were no significant relationships between PheO-NAC levels and the occurrence of two GSTP1 polymorphisms. The results of this study provide the first evidence for a PAH-derived mercapturic acid in human urine and should be useful in the development of a phenotyping approach to assess individual differences in PAH metabolism.

Chromatography, High Pressure Liquid↗
PubMed2006

Analysis of crotonaldehyde- and acetaldehyde-derived 1,n(2)-propanodeoxyguanosine adducts in DNA from human tissues using liquid chromatography electrospray ionization tandem mass spectrometry.

Crotonaldehyde, a mutagen and carcinogen, reacts with deoxyguanosine (dGuo) in DNA to generate a pair of diastereomeric 1,N(2)()-propanodeoxyguanosine adducts (Cro-dGuo, 2), which occur in (6S,8S) and (6R,8R) configurations. They can also be formed through the consecutive reaction of two acetaldehyde molecules with dGuo. Cro-dGuo adducts inhibit DNA synthesis and induce miscoding in human cells. Considering their potential role in carcinogenesis, we have developed a sensitive and specific liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method to explore the presence of Cro-dGuo adducts in DNA from various human tissues, such as liver, lung, and blood. DNA was isolated from human tissues and enzymatically hydrolyzed to deoxyribonucleosides. [(15)N(5)]Cro-dGuo was synthesized and used as an internal standard. The Cro-dGuo adducts were enriched from the hydrolysate by solid-phase extraction and analyzed by LC-ESI-MS/MS using selected reaction monitoring (SRM). This method allows the quantitation of the Cro-dGuo adducts at a concentration of 4 fmol/micromol dGuo, corresponding to about 1 adduct per 10(9) normal nucleosides starting with 1 mg of DNA, with high accuracy and precision. DNA from human liver, lung, and blood was analyzed. The Cro-dGuo adducts were detected more frequently in human lung DNA than in liver DNA but were not detected in DNA from blood. The results of this study provide quantified data on Cro-dGuo adducts in human tissues. The higher frequency of Cro-dGuo in lung DNA than in the other tissues investigated is potentially important and deserves further study.

Acetaldehyde↗
PubMed2006

Tobacco-specific nitrosamines in new tobacco products.

New tobacco products, designed to attract consumers who are concerned about the health effects of tobacco, have been appearing on the market. Objective evaluation of these products requires, as a first step, data on their potentially toxic constituents. Tobacco-specific nitrosamines (TSNAs) are an important class of carcinogens in tobacco products, but virtually no data were available on their levels in these products. In the present study, we analyzed several new products-Ariva, Stonewall, Exalt, Revel, Smokey Mountain, and Quest-for TSNAs and compared their TSNA levels with those in nicotine replacement products and conventional smokeless tobacco and cigarette brands. TSNAs were not detected in Smokey Mountain, which is a tobacco-free snuff product. The lowest levels among the new products containing tobacco were in Ariva and Stonewall (0.26-0.28 microg/g wet weight of product). The highest levels in the new products were found in Exalt (3.3 microg/g tobacco), whereas Revel and Quest had intermediate amounts. Only trace amounts were found in nicotine replacement products, and conventional brands had levels consistent with those reported in the literature. These results demonstrate that TSNA levels in new tobacco products range from relatively low to comparable with those found in some conventional brands.

Carcinogenicity Tests↗
PubMed2006

Biomarkers to assess the utility of potential reduced exposure tobacco products.

To date, we have no valid biomarkers that serve as proxies for tobacco-related disease to test potential reduced exposure products. This paper represents the deliberations of four workgroups that focused on four tobacco-related heath outcomes: Cancer, nonmalignant pulmonary disease, cardiovascular disease, and fetal toxicity. The goal of these workgroups was to identify biomarkers that offer some promise as measures of exposure or toxicity and ultimately may serve as indicators for future disease risk. Recommendations were based on the relationship of the biomarker to what is known about mechanisms of tobacco-related pathogenesis, the extent to which the biomarker differs among smokers and nonsmokers, and the sensitivity of the biomarker to changes in smoking status. Other promising biomarkers were discussed. No existing biomarkers have been demonstrated to be predictive of tobacco-related disease, which highlights the importance and urgency of conducting research in this area.

Biomarkers↗
PubMed2006

Biomarkers to assess the utility of potential reduced exposure tobacco products.

To date, we have no valid biomarkers that serve as proxies for tobacco-related disease to test potential reduced exposure products. This paper represents the deliberations of four workgroups that focused on four tobacco-related heath outcomes: Cancer, nonmalignant pulmonary disease, cardiovascular disease, and fetal toxicity. The goal of these workgroups was to identify biomarkers that offer some promise as measures of exposure or toxicity and ultimately may serve as indicators for future disease risk. Recommendations were based on the relationship of the biomarker to what is known about mechanisms of tobacco-related pathogenesis, the extent to which the biomarker differs among smokers and nonsmokers, and the sensitivity of the biomarker to changes in smoking status. Other promising biomarkers were discussed. No existing biomarkers have been demonstrated to be predictive of tobacco-related disease, which highlights the importance and urgency of conducting research in this area.

Biomarkers↗
PubMed2006

Uptake of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by Moldovan children.

The evidence of an association between childhood exposure to environmental tobacco smoke (ETS) and an increased risk of lung cancer is inconsistent. However, taking into account the existing association between lung cancer and adulthood ETS exposure, it is plausible that children exposed to ETS also would be at risk of developing lung cancer later in life. In this study, we investigated the uptake by Moldovan children of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by measuring total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), the sum of the NNK metabolites, NNAL, and its O-glucuronide and N-glucuronide (NNAL-Glucs) in urine. We also measured urinary cotinine and its glucuronide (total cotinine). Total NNAL was detected in 69 of 80 samples, including those that were low in cotinine (<5 ng/mL). The mean+/- SD level of total NNAL (0.09+/- 0.077 pmol/mL) was comparable with those observed in previous studies of children and adults exposed to ETS. Total NNAL correlated with total cotinine (r=0.8, P<0.0001). The mean+/- SD levels of total NNAL and total cotinine were higher in children who were exposed to ETS (0.1+/- 0.08 and 109+/- 126 pmol/mL, respectively) than in those who were classified as unexposed to ETS based on questionnaire data (0.049+/- 0.016 pmol/mL and 0.043+/- 0.040 nmol/mL). The results of this study for the first time show widespread and considerable uptake of nicotine and the tobacco-specific lung carcinogen NNK in Moldovan children. These results should be useful in heightening the awareness of the dangers of smoking and ETS exposure in this eastern European country.

Adenocarcinoma↗