| مستخلص: |
Our study objectives were (1) to investigate the selectivityofpolycyclic aromatic hydrocarbon (PAH) metabolites for tobacco smokeexposure 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-liveswere determined in 8 smokers. In controlled hospital studies of 18smokers, the associations between various measures of nicotine intakeand urinary excretion of PAH metabolites were investigated. Plasmanicotine was measured by GC. LC-MS/MS was used to measure the plasmalevels 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). Regardlessof smoking status, PAH metabolite excretion was higher in Polish subjectsthan in US subjects (p-values <0.001). 1-Hydroxyfluoreneexhibited the greatest difference between smokers and nonsmokers,with a 5-fold difference in Polish subjects and a 25-fold differencein US subjects, followed by 3- and 2-hydroxyfluorenes, 2-naphthol,and 1-hydroxypyrene. The differences for hydroxyphenanthrenes weresmall or nonsignificant. 1-Hydroxyfluorene had the highest correlationwith urine nicotine equivalents (r= 0.77) and urineNNAL (r= 0.64). While the half-lives of PAH metaboliteswere <10 h in smokers, 1-hydroxyfluorene had the largest ratioof 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 thathydroxyfluorenes are most highly discriminative of smokers from nonsmokersfollowed by 2-naphthol and 1-hydroxypyrene. In conclusion, hydroxyfluorenes,particularly 1-hydroxyfluorene, and 2-naphthol are more selectiveof tobacco smoke than 1-hydroxypyrene and hydroxyphenanthrenes. Characterizationof hydroxyfluorene and 2-naphthol metabolites in urine may improvethe characterization of PAHs from tobacco smoke and related diseaserisks among smokers and nonsmokers. [ABSTRACT FROM AUTHOR] |
