title: 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.
abstract: 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.
authors.forename: Meng
authors.initials: M
authors.lastname: Huang
authors.forename: Clementina
authors.initials: C
authors.lastname: Mesaros
authors.affiliation: Synthetic Organic Chemistry Core, Center in Environmental Toxicology, University of Texas Medical Branch at Galveston , Galveston, Texas 77555-1110, United States.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Hackfeld
authors.affiliation: Synthetic Organic Chemistry Core, Center in Environmental Toxicology, University of Texas Medical Branch at Galveston , Galveston, Texas 77555-1110, United States.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hodge
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Zang
authors.forename: Ian A
authors.initials: IA
authors.lastname: Blair
authors.forename: Trevor M
authors.identifier: 0000-0002-3937-1066
authors.initials: TM
authors.lastname: Penning
mesh_terms: D000449:Aldehyde Reductase / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D000478:Alkylation; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002396:Catechols / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D020387:Food Chain; D056945:Hep G2 Cells; D006801:Humans; D059392:Petroleum Pollution; D010616:Phenanthrenes / Q000032:analysis* / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry
chemical_list: D002396:Catechols; D010616:Phenanthrenes; D011084:Polycyclic Aromatic Hydrocarbons; C447880:retene; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D002394:Catechol O-Methyltransferase