Elevated levels of volatile organic carcinogen and toxicant biomarkers in Chinese women who regularly cook at home.

Background: Epidemiologic studies associate lung cancer in nonsmoking Chinese women with Chinese-style wok cooking. Our goal was to quantify carcinogen and toxicant biomarkers in Chinese women who reported regularly doing home cooking compared with women randomly selected from the Singapore Chinese Health Study as controls.

Methods: Biomarkers were quantified by high-performance liquid chromatography-mass spectrometry, high-performance liquid chromatography with fluorescence detection, and gas chromatography-mass spectrometry.

Temporal stability of urinary and plasma biomarkers of tobacco smoke exposure among cigarette smokers.

Intraindividual variability of measurements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), nicotine, cotinine, and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) over time is uncertain. From 70 habitual smokers' plasma and urine sampled bimonthly for a year we analysed plasma for NNAL, cotinine and PheT, and urine for NNAL, cotinine and nicotine. We estimated the intraclass correlation coefficients (rho(I)) for each measurement.

Analysis of phenanthrene and benzo[a]pyrene tetraol enantiomers in human urine: relevance to the bay region diol epoxide hypothesis of benzo[a]pyrene carcinogenesis and to biomarker studies.

One widely accepted metabolic activation pathway of the prototypic carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) proceeds through the "bay region diol epoxide" BaP-(7R,8S)-diol-(9S,10R)-epoxide (2). However, few studies have addressed the analysis of human urinary metabolites of BaP, which result from this pathway. Phenanthrene (Phe) is structurally related to BaP, but human exposure to Phe is far greater, and its metabolites can be readily detected in urine.

Formation and distribution of NNK metabolites in an isolated perfused rat lung.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a lung-specific tobacco carcinogen. Metabolism is critical to its elimination given its lipophilic nature. Although NNK can be metabolized through detoxification pathways that safely eliminate it from the body, it can also be bioactivated, resulting in the formation of potentially carcinogenic DNA adducts.

Abstinence and relapse rates following a college campus-based quit & win contest.

Objective: To conduct and evaluate Quit & Win contests at 2 2-year college and 2 4-year university campuses.

Participants: During Spring semester, 2006, undergraduates (N = 588) interested in quitting smoking signed up for a Quit & Win 30-day cessation contest for a chance to win a lottery prize.

Methods: Participants (N = 588) completed a baseline survey, provided a urine sample to verify smoking status before joining the contest, and completed a follow-up survey at contest end to assess abstinence.

Berry ellagitannins may not be sufficient for prevention of tumors in the rodent esophagus.

Biodirected fractionation is used to identify the active inhibitory constituents in berries for esophageal cancer in rats. The present study was undertaken to determine if ellagitannins contribute to the chemopreventive activity of an alcohol/water-insoluble (residue) fraction of berries. Rats consumed diets containing residue fractions of three berry types, that is, black raspberries (BRBs), strawberries (STRWs), and blueberries (BBs), that differ in their content of ellagitannins in the order BRB > STRW > BB.

Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation.

Aims: To examine the effects of reduced nicotine cigarettes on smoking behavior, toxicant exposure, dependence and abstinence.

Design: Randomized, parallel arm, semi-blinded study. Setting University of Minnesota Tobacco Use Research Center.

Interaction of CYP1B1, cigarette-smoke carcinogen metabolism, and lung cancer risk.

A previously published case-control study nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial found a significant relationship of serum levels of total NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides) to prospective lung cancer risk. The present paper examines this relationship in the context of single-nucleotide polymorphisms (SNPs) in genes important in the metabolism of tobacco smoke carcinogens. DNA was extracted from the subjects' lymphocytes and analyzed for SNPs in 11 locations on four genes related to tobacco carcinogen metabolism.

Analysis of 23 polycyclic aromatic hydrocarbons in smokeless tobacco by gas chromatography-mass spectrometry.

Smokeless tobacco contains 28 known carcinogens and causes precancerous oral lesions and oral and pancreatic cancer. A recent study conducted by our research team identified eight different polycyclic aromatic hydrocarbons (PAHs) in U.S.

Eukaryotic initiation factor 4E binding protein family of proteins: sentinels at a translational control checkpoint in lung tumor defense.

The usurping of translational control by sustained activation of translation initiation factors is oncogenic. Here, we show that the primary negative regulators of these oncogenic initiation factors--the 4E-BP protein family--operate as guardians of a translational control checkpoint in lung tumor defense. When challenged with the tobacco carcinogen 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone (NNK), 4ebp1(-/-)/4ebp2(-/-) mice showed increased sensitivity to tumorigenesis compared with their wild-type counterparts.

Presence of the carcinogen N'-nitrosonornicotine in the urine of some users of oral nicotine replacement therapy products.

N'-nitrosonornicotine (NNN) is a strong carcinogen present in unburned tobacco and cigarette smoke. We here analyze data obtained in two studies, in which a biomarker of exposure to NNN--the sum of NNN and its pyridine-N-glucuronide, called total NNN--was quantified in the urine of people who had stopped smoking and used various nicotine replacement therapy (NRT) products. In 13 of 34 nicotine gum or lozenge users from both studies, total NNN at one or more time points after biochemically confirmed smoking cessation was comparable with, or considerably higher than, the baseline levels.

Formaldehyde and leukemia: epidemiology, potential mechanisms, and implications for risk assessment.

Formaldehyde is widely used in the United States and other countries. Occupational and environmental exposures to formaldehyde may be associated with an increased risk of leukemia in exposed individuals. However, risk assessment of formaldehyde and leukemia has been challenging due to inconsistencies in human and animal studies and the lack of a known mechanism for leukemia induction.

Mass spectrometric analysis of a cyclic 7,8-butanoguanine adduct of N-nitrosopyrrolidine: comparison to other N-nitrosopyrrolidine adducts in rat hepatic DNA.

The well established rat hepatocarcinogen N-nitrosopyrrolidine (NPYR, 1) requires metabolic activation to DNA adducts to express its carcinogenic activity. Among the NPYR-DNA adducts that have been identified, the cyclic 7,8-butanoguanine adduct 2-amino-6,7,8,9-tetrahydro-9-hydroxypyrido[2,1-f]purine-4(3H)-one (6) has been quantified using moderately sensitive methods, but its levels have never been compared to those of other DNA adducts of NPYR in rat hepatic DNA. Therefore, in this study, we developed a sensitive new LC-ESI-MS/MS-SRM method for the quantitation of adduct 6 and compared its levels to those of several other NPYR-DNA adducts formed by different mechanisms.

Clear differences in levels of a formaldehyde-DNA adduct in leukocytes of smokers and nonsmokers.

Formaldehyde is considered carcinogenic to humans by the IARC, but there are no previous reports of formaldehyde-DNA adducts in humans. In this study, we used liquid chromatography-electrospray ionization-tandem mass spectrometry to quantify the formaldehyde-DNA adduct N(6)-hydroxymethyldeoxyadenosine (N(6)-HOMe-dAdo) in leukocyte DNA samples from 32 smokers of >or=10 cigarettes per day and 30 nonsmokers. Clear peaks coeluting with the internal standard in two different systems were seen in samples from smokers but rarely in nonsmokers.

Inhibition of vinyl carbamate-induced pulmonary adenocarcinoma by indole-3-carbinol and myo-inositol in A/J mice.

In previous studies, we reported that indole-3-carbinol (I3C) and myo-inositol (MI) inhibit lung adenoma induced by tobacco smoke carcinogens in A/J mice. In this paper, we extended our work and examined the effects of I3C (70 or 30 micromol/g diet) and MI (56 micromol/g diet) against vinyl carbamate (VC)-induced lung adenocarcinoma by administering the agents from 1 week after the second of two injections of VC until termination of the study at week 18. The higher dose of I3C decreased multiplicities of tumors on the surface of the lung (26%, P = 0.

Exposure to the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers from 3 populations with different risks of lung cancer.

Native Hawaiian smokers are at higher risk and Japanese-American smokers at lower risk of lung cancer (LC), compared with white smokers, even after accounting for smoking history. Because variation in carcinogen exposure/metabolism may occur separately of smoking amount, we compared urinary biomarkers of uptake and detoxification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-a potent lung carcinogen-among 578 smokers in these ethnic/racial groups in Hawaii. We measured the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc) and examined total NNAL (NNAL + NNAL-Gluc) and the NNAL detoxification ratio (NNAL-Gluc:NNAL).

Chemoprevention of lung carcinogenesis in addicted smokers and ex-smokers.

Chemoprevention of lung carcinogenesis is one approach to controlling the epidemic of lung cancer caused by cigarette smoking. The target for chemoprevention should be the activities of the multiple carcinogens, toxicants, co-carcinogens, tumour promoters and inflammatory compounds in cigarette smoke. At present there are many agents, both synthetic and naturally occurring, that prevent lung tumour development in well-established animal models.

Quantitation of pyridyloxobutyl DNA adducts in nasal and oral mucosa of rats treated chronically with enantiomers of N'-nitrosonornicotine.

N'-Nitrosonornicotine (NNN) is one of the most important strong carcinogens in tobacco products and is believed to play a significant role in the induction of esophageal cancer in smokers and oral cavity cancer in snuff dippers. NNN is metabolically activated through cytochrome P450-catalyzed alpha-hydroxylation. 2'-Hydroxylation produces a reactive intermediate 4-(3-pyridyl)-4-oxobutanediazohydroxide (7), which alkylates DNA to form pyridyloxobutyl (POB)-DNA adducts.

Analysis of pyridyloxobutyl and pyridylhydroxybutyl DNA adducts in extrahepatic tissues of F344 rats treated chronically with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are potent pulmonary carcinogens in rats. NNK and NNAL require metabolic activation to express their carcinogenicity. Cytochrome P450-catalyzed alpha-hydroxylation at the methyl position of NNK or NNAL generates reactive intermediates, which alkylate DNA to form pyridyloxobutyl (POB)-DNA adducts or pyridylhydroxybutyl (PHB)-DNA adducts.

Comparative levels of O6-methylguanine, pyridyloxobutyl-, and pyridylhydroxybutyl-DNA adducts in lung and liver of rats treated chronically with the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a lung carcinogen in rats and may be a cause of lung cancer in smokers. NNK is metabolized by cytochromes P450 to intermediates that react with DNA forming methyl, pyridyloxobutyl (POB), and pyridylhydroxybutyl (PHB) adducts, which are critical in carcinogenesis. The methyl adduct O(6)-methylguanine (O(6)-methyl-G) has miscoding properties, but there are no reports on levels of this adduct in rats treated chronically with NNK in the drinking water, nor has its levels been compared with those of POB- and PHB-DNA adducts.

Urinary levels of tobacco-specific nitrosamine metabolites in relation to lung cancer development in two prospective cohorts of cigarette smokers.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (sum of which is denoted as total NNAL) are metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK and NNAL can induce lung cancer in laboratory animals but human data are limited. The association between prediagnostic levels of urinary total NNAL and risk of lung cancer development was evaluated in two prospective cohorts of Chinese cigarette smokers.

Effects of smoking cessation on eight urinary tobacco carcinogen and toxicant biomarkers.

We determined the persistence at various times (3, 7, 14, 21, 28, 42, and 56 days) of eight tobacco smoke carcinogen and toxicant biomarkers in the urine of 17 smokers who stopped smoking. The biomarkers were 1-hydroxy-2-(N-acetylcysteinyl)-3-butene (1) and 1-(N-acetylcysteinyl)-2-hydroxy-3-butene (2) [collectively called MHBMA for monohydroxybutyl mercapturic acid] and 1,2-dihydroxy-4-(N-acetylcysteinyl)butane (3) [DHBMA for dihydroxybutyl mercapturic acid], metabolites of 1,3-butadiene; 1-(N-acetylcysteinyl)-propan-3-ol (4, HPMA for 3-hydroxypropyl mercapturic acid), a metabolite of acrolein; 2-(N-acetylcysteinyl)butan-4-ol (5, HBMA for 4-hydroxybut-2-yl mercapturic acid), a metabolite of crotonaldehyde; (N-acetylcysteinyl)benzene (6, SPMA for S-phenyl mercapturic acid), a metabolite of benzene; (N-acetylcysteinyl)ethanol (7, HEMA for 2-hydroxyethyl mercapturic acid), a metabolite of ethylene oxide; 1-hydroxypyrene (8) and its glucuronides (1-HOP), metabolites of pyrene; and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (9) and its glucuronides (total NNAL), a biomarker of exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These biomarkers represent some of the major carcinogens and toxicants in cigarette smoke: 1,3-butadiene, acrolein, crotonaldehyde, benzene, ethylene oxide, polycyclic aromatic hydrocarbons (PAH), and NNK.

Evidence for endogenous formation of N'-nitrosonornicotine in some long-term nicotine patch users.

Introduction: Nitrosation of nicotine or its metabolites in the human body could lead to formation of the 2 carcinogenic tobacco-specific nitrosamines-N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

Methods: We investigated the possibility of endogenous formation of NNN in people who had stopped smoking and used the 21-mg nicotine patch for 6 months. We quantified urinary biomarkers of exposure to NNN-the sum of NNN and its pyridine-N-glucuronide, referred to as total NNN.