Metabolism of a representative oxygenated polycyclic aromatic hydrocarbon (PAH) phenanthrene-9,10-quinone in human hepatoma (HepG2) cells.

Exposure to polycyclic aromatic hydrocarbons (PAHs) in the food chain is the major human health hazard associated with the Deepwater Horizon oil spill. Phenanthrene is a representative PAH present in crude oil, and it undergoes biological transformation, photooxidation, and chemical oxidation to produce its signature oxygenated derivative, phenanthrene-9,10-quinone. We report the downstream metabolic fate of phenanthrene-9,10-quinone in HepG2 cells. The structures of the metabolites were identified by HPLC–UV–fluorescence detection and LC–MS/MS. O-mono-Glucuronosyl-phenanthrene-9,10-catechol was identified, as reported previously. A novel bis-conjugate, O-mono-methyl-O-mono-sulfonated-phenanthrene-9,10-catechol, was discovered for the first time, and evidence for both of its precursor mono conjugates was obtained. The identities of these four metabolites were unequivocally validated by comparison to authentic enzymatically synthesized standards. Evidence was also obtained for a minor metabolic pathway of phenanthrene-9,10-quinone involving bis-hydroxylation followed by O-mono-sulfonation. The identification of 9,10-catechol conjugates supports metabolic detoxification of phenanthrene-9,10-quinone through interception of redox cycling by UGT, COMT, and SULT isozymes and indicates the possible use of phenanthrene-9,10-catechol conjugates as biomarkers of human exposure to oxygenated PAH.

食物链中多环芳烃（PAHs）暴露是与“深水地平线”石油泄漏相关的主要人类健康危害。菲是原油中存在的一种具有代表性的多环芳烃，它会经历生物转化、光氧化和化学氧化，产生其标志性的含氧衍生物菲 - 9,10 - 醌。我们报道了菲 - 9,10 - 醌在HepG2细胞中的下游代谢归宿。通过高效液相色谱 - 紫外 - 荧光检测和液相色谱 - 质谱/质谱联用技术确定了代谢物的结构。如先前报道，鉴定出了O - 单 - 葡萄糖醛酸苷 - 菲 - 9,10 - 儿茶酚。首次发现了一种新型的双共轭物，O - 单 - 甲基 - O - 单 - 磺化 - 菲 - 9,10 - 儿茶酚，并且获得了其两种前体单共轭物的证据。通过与真实的酶促合成标准品比较，明确验证了这四种代谢物的身份。还获得了菲 - 9,10 - 醌的一条次要代谢途径的证据，该途径涉及双羟基化，随后是O - 单 - 磺化。9,10 - 儿茶酚共轭物的鉴定支持了菲 - 9,10 - 醌通过尿苷二磷酸葡萄糖醛酸转移酶（UGT）、儿茶酚 - O - 甲基转移酶（COMT）和磺基转移酶（SULT）同工酶阻断氧化还原循环进行代谢解毒，并表明菲 - 9,10 - 儿茶酚共轭物可能用作人类暴露于含氧多环芳烃的生物标志物。