Polycyclic aromatic hydrocarbons (PAH) are well-established environmental carcinogens likely to be causative agents for some human cancers. Bay-region diol epoxides are ultimate carcinogenic metabolites of multiple PAH. Dihydrodiols are the important intermediate products of this pathway and can be further oxidized to form diol epoxides. We quantified two dihydrodiol metabolites of phenanthrene (Phe), the simplest PAH with a bay-region, in the 6 h urine of smokers (N = 25) and non-smokers (N = 25) using a newly developed and validated analytical method. After hydrolysis by ß-glucuronidase and sulfatase, and solid phase extraction, the sample was silylated and analyzed by gas chromatography-negative ion chemical ionization-tandem mass spectrometry (GC-NICI-MS/MS). Levels (nmol/6h urine) of Phe-1,2-dihydrodiol (Phe-1,2-D) and Phe-3,4-dihydrodiol (Phe-3,4-D) were 2.04 ± 1.52 and 0.51 ± 0.35 , respectively, in smokers, significantly higher than those in non-smokers (1.35 ± 1.11 of Phe-1,2-D, p < 0.05; 0.27 ± 0.25 of Phe-3,4-D, p < 0.005). Cigarette smoking also influenced the regioselective metabolism of Phe, presenting as a significant difference in the urinary distribution pattern of Phe-1,2-D and Phe-3,4-D between smokers and non-smokers: the ratio Phe-3,4-D: Phe-1,2-D increased from 0.20 in non-smokers to 0.28 in smokers (p < 0.01), which can be explained by the induction of the phenanthrene metabolizing enzymes CYP1A2 and CYP1B1 by cigarette smoke. The method described here is the first example of facile quantitation of an intact human dihydrodiol metabolite of any PAH with three or more aromatic rings and will be applicable in clinical and molecular epidemiology studies of PAH metabolism and cancer susceptibility.

中文翻译：

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气相色谱-负离子化学电离-串联质谱法定量测定吸烟者和非吸烟者尿液中的菲二氢二醇。

多环芳烃（PAH）是公认的环境致癌物，可能是某些人类癌症的病原体。湾区二醇环氧化物是多种PAH的最终致癌代谢产物。二氢二醇是该途径的重要中间产物，并且可以被进一步氧化以形成二醇环氧化物。我们使用一种新开发和验证的分析方法，在吸烟者（N = 25）和非吸烟者（N = 25）的6 h尿液中，量化了菲（Phe）中最简单的具有海湾区域的PAH的两种二氢二醇代谢物。经ß-葡糖醛酸苷酶和硫酸酯酶水解，固相萃取后，将样品甲硅烷基化并通过气相色谱-负离子化学电离-串联质谱法（GC-NICI-MS / MS）进行分析。Phe-1,2-二氢二醇（Phe-1,2-D）和Phe-3的水平（nmol / 6h尿液），吸烟者中的4-二氢二醇（Phe-3,4-D）分别为2.04±1.52和0.51±0.35，明显高于非吸烟者（Phe-1,2-D的1.35±1.11，p <0.05 ； Phe-3,4-D的0.27±0.25，p <0.005）。吸烟还影响了Phe的区域选择性代谢，在吸烟者和非吸烟者之间，Phe-1,2-D和Phe-3,4-D的尿液分布模式存在显着差异：比率Phe-3,4 -D：Phe-1,2-D从非吸烟者的0.20升高到吸烟者的0.28（p <0.01），这可以通过香烟烟雾中菲代谢酶CYP1A2和CYP1B1的诱导来解释。