title: Exposure and kinetics of polycyclic aromatic hydrocarbons (PAHs) in cigarette smokers.
abstract: Our study objectives were (1) to investigate the selectivity of polycyclic aromatic hydrocarbon (PAH) metabolites for tobacco smoke exposure and (2) to determine half-lives of PAH metabolites in smokers. There were 622 participants from the United States (US) and Poland, and of these, 70% were smokers. All subjects provided spot urine samples, and 125 smokers provided blood samples. Urinary PAH metabolite half-lives were determined in 8 smokers. In controlled hospital studies of 18 smokers, the associations between various measures of nicotine intake and urinary excretion of PAH metabolites were investigated. Plasma nicotine was measured by GC. LC-MS/MS was used to measure the plasma levels of cotinine and trans-3'-hydroxycotinine, and urine levels of nicotine and its metabolites, total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and PAH metabolites (2-naphthol, 1-, 2-, and 3-hydroxyfluorenes, 1-, 2-, 3-, and 4-hydroxyphenanthrenes, and 1-hydroxypyrene). Regardless of smoking status, PAH metabolite excretion was higher in Polish subjects than in US subjects (p-values <0.001). 1-Hydroxyfluorene exhibited the greatest difference between smokers and nonsmokers, with a 5-fold difference in Polish subjects and a 25-fold difference in US subjects, followed by 3- and 2-hydroxyfluorenes, 2-naphthol, and 1-hydroxypyrene. The differences for hydroxyphenanthrenes were small or nonsignificant. 1-Hydroxyfluorene had the highest correlation with urine nicotine equivalents (r = 0.77) and urine NNAL (r = 0.64). While the half-lives of PAH metabolites were <10 h in smokers, 1-hydroxyfluorene had the largest ratio of initial to terminal urine concentration (58.4 ± 38.6, mean ± SD) after smoking. Receiver Operating Characteristic (ROC) analysis of PAHs among Polish and US subjects further showed that hydroxyfluorenes are most highly discriminative of smokers from nonsmokers followed by 2-naphthol and 1-hydroxypyrene. In conclusion, hydroxyfluorenes, particularly 1-hydroxyfluorene, and 2-naphthol are more selective of tobacco smoke than 1-hydroxypyrene and hydroxyphenanthrenes. Characterization of hydroxyfluorene and 2-naphthol metabolites in urine may improve the characterization of PAHs from tobacco smoke and related disease risks among smokers and nonsmokers.
authors.affiliation: Center for Tobacco Control Research and Education, University of California, San Francisco, California, USA.
authors.forename: Gideon
authors.initials: G
authors.lastname: St Helen
authors.forename: Maciej L
authors.initials: ML
authors.lastname: Goniewicz
authors.forename: Delia
authors.initials: D
authors.lastname: Dempsey
authors.forename: Margaret
authors.initials: M
authors.lastname: Wilson
authors.forename: Peyton
authors.initials: P
authors.lastname: Jacob
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003367:Cotinine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000378:metabolism / Q000652:urine; D009602:Nitrosamines / Q000652:urine; D011044:Poland; D011084:Polycyclic Aromatic Hydrocarbons / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011725:Pyridines / Q000652:urine; D012372:ROC Curve; D012907:Smoking; D053719:Tandem Mass Spectrometry; D014481:United States; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009602:Nitrosamines; D011084:Polycyclic Aromatic Hydrocarbons; D011725:Pyridines; C001381:hydroxycotinine; D009538:Nicotine; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol; D003367:Cotinine