Waidyanatha Suramya, Rothman Nathaniel, Li Guilan, Smith Martyn T, Yin Songnian, Rappaport Stephen M
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7431, USA.
Anal Biochem. 2004 Apr 15;327(2):184-99. doi: 10.1016/j.ab.2004.01.008.
A gas chromatography-mass spectrometry method for measurement of the main urinary metabolites of benzene, namely, phenol, catechol, hydroquinone, 1,2,4-trihydroxybenzene (trihydroxybenzene), t,t-muconic acid (muconic acid), and S-phenylmercapturic acid (phenylmercapturic acid), is reported. The method is considerably simpler than existing assays. It was applied to urine from benzene-exposed subjects and controls from Shanghai, China. When subjects were divided into controls (n = 44), those exposed to </= 31 ppm benzene (n = 21), and those exposed to > 31 ppm benzene (n = 19), Spearman correlations with exposure category were >/= 0.728 (p < 0.0001) for all metabolites except trihydroxybenzene. When exposed subjects were compared on an individual basis, all metabolites, including trihydroxybenzene, were significantly correlated with benzene exposure (Pearson r >/= 0.472, p </= 0.002) and with each other (Pearson r >/= 0.708, p < 0.0001). Ratios of individual metabolite levels to total metabolite levels provided evidence of competitive inhibition of CYP 2E1 enzymes leading to increased production of phenol, catechol, and phenylmercapturic acid at the expense of hydroquinone, trihydroxybenzene, and muconic acid. Since all metabolites were detected in all control subjects, the method can be applied to persons exposed to environmental levels of benzene.
本文报道了一种气相色谱 - 质谱法，用于测定苯的主要尿代谢产物，即苯酚、儿茶酚、对苯二酚、1,2,4 - 三羟基苯（三羟基苯）、反,反 - 粘康酸（粘康酸）和S - 苯基巯基尿酸（苯基巯基尿酸）。该方法比现有检测方法要简单得多。它被应用于来自中国上海的苯暴露受试者和对照组的尿液样本。当将受试者分为对照组（n = 44）、苯暴露水平≤31 ppm的受试者（n = 21）和苯暴露水平> 31 ppm的受试者（n = 19）时，除三羟基苯外，所有代谢产物与暴露类别之间的斯皮尔曼相关性均≥0.７28（p < 0.0001）。当对暴露受试者进行个体比较时，所有代谢产物，包括三羟基苯，均与苯暴露显著相关（皮尔逊r≥0.472，p≤0.002），且彼此之间也显著相关（皮尔逊r≥0.708，p < 0.0001）。个体代谢产物水平与总代谢产物水平的比值提供了细胞色素P450 2E1酶竞争性抑制的证据，这种抑制导致苯酚、儿茶酚和苯基巯基尿酸的生成增加，而对苯二酚、三羟基苯和粘康酸的生成减少。由于在所有对照受试者中均检测到了所有代谢产物，因此该方法可应用于暴露于环境水平苯的人群。
