Potential Metabolic Activation of a Representative C4-Alkylated Polycyclic Aromatic Hydrocarbon Retene (1-Methyl-7-isopropyl-phenanthrene) Associated with the Deepwater Horizon Oil Spill in Human Hepatoma (HepG2) Cells

• Published in: Chemical research in toxicology Vol. 30; no. 4; pp. 1093 - 1101
• Main Authors: Huang, Meng, Mesaros, Clementina, Hackfeld, Linda C, Hodge, Richard P, Zang, Tianzhu, Blair, Ian A, Penning, Trevor M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17-04-2017
• Subjects: Aldehyde Reductase - metabolism; Aldo-Keto Reductases; Alkylation; Catechol O-Methyltransferase - metabolism; Catechols - chemistry; Chromatography, High Pressure Liquid; Food Chain; Hep G2 Cells; Humans; Petroleum Pollution; Phenanthrenes - analysis; Phenanthrenes - metabolism; Polycyclic Aromatic Hydrocarbons - chemistry; Polycyclic Aromatic Hydrocarbons - metabolism; Spectrophotometry, Ultraviolet; Tandem Mass Spectrometry
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/acs.chemrestox.6b00457

Exposure to petrogenic polycyclic aromatic hydrocarbons (PPAHs) in the food chain is the major human health hazard associated with the Deepwater Horizon oil spill. C4-Phenanthrenes are representative PPAHs present in the crude oil and could contaminate the seafood. We describe the metabolism of a C4-phenanthrene regioisomer retene (1-methyl-7-isopropyl-phenanthrene) in human HepG2 cells as a model for metabolism in human hepatocytes. Retene because of its sites of alkylation cannot be metabolized to a diol-epoxide. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC–MS/MS. O-Monosulfonated-retene-catechols were discovered as signature metabolites of the ortho-quinone pathway of PAH activation catalyzed by aldo-keto reductases. We also found evidence for the formation of bis-ortho-quinones where the two dicarbonyl groups were present on different rings of retene. The identification of O-monosulfonated-retene-catechol and O-bismethyl-O-monoglucuronosyl-retene-bis-catechol supports metabolic activation of retene by P450 and aldo-keto reductase isozymes followed by metabolic detoxification of the ortho-quinone through interception of redox cycling by catechol-O-methyltransferase, uridine 5′-diphospho-glucuronosyltransferase, and sulfotransferase isozymes. We propose that catechol conjugates could be used as biomarkers of human exposure to retene resulting from oil spills.