Phenanthrene is the simplest polycyclic aromatic hydrocarbon (PAH) containing a bay region, a feature closely associated with carcinogenicity. We have proposed that measurement of phenanthrene metabolites in human urine could be used to identify interindividual differences in metabolic activation and detoxification of PAH, and that these differences may be related to cancer susceptibility in smokers and other exposed individuals. Previously, we reported a method for quantitation of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4- tetrahydrophenanthrene (trans, anti-PheT) in human urine, trans, anti-PheT is the ultimate product of the diol epoxide metabolic activation pathway of phenanthrene. In this study, we have extended our carcinogen metabolite phenotyping approach by developing a method for quantitation of phenanthrols in human urine. PAH phenols such as phenanthrols are considered as detoxification products. After treatment of the urine by β-glucuronidase and arylsulfatase, a fraction enriched in phenanthrols was prepared by partitioning and solid phase extraction. The phenanthrols were silylated and analyzed by gas chromatography-positive ion chemical ionization-mass spectrometry with selected ion monitoring. [ring-13C6]3-phenanthrol was used as an internal standard. Accurate and reproducible quantitation of four phenanthrols, 1-phenanthrol (1-HOPhe), 2-HOPhe, 3-HOPhe, and 4-HOPhe, was readily achieved. In smokers, mean levels of 1-HOPhe (0.96 ± 1.2 pmol/mg creatinine) and 3-HOPhe (0.82 ± 0.62 pmol/mg creatinine) were greater than those of 2-HOPhe (0.47 ± 0.29 pmol/mg creatinine), and 4-HOPhe (0.11 ± 0.07 pmol/mg creatinine). There were no significant differences between the levels of any of the phenanthrols in smokers and nonsmokers. Total levels of the quantified phenanthrols were highly correlated with those of 3-HOPhe. Ratios of phenanthrene metabolites representing activation and detoxification were calculated as trans, anti-PheT divided by 3-HOPhe. There was a 7.5-fold spread of ratios in smokers, and a 12.3-fold spread in nonsmokers, suggesting that this may be a useful parameter for distinguishing individual metabolic responses to PAH exposure.
|Original language||English (US)|
|Number of pages||8|
|Journal||Cancer Epidemiology Biomarkers and Prevention|
|State||Published - Dec 2004|