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

Chem Res Toxicol. 2017 Apr 17;30(4):1093-1101. doi: 10.1021/acs.chemrestox.6b00457. Epub 2017 Mar 22.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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


  • Catechols
  • Phenanthrenes
  • Polycyclic Aromatic Hydrocarbons
  • retene
  • Aldo-Keto Reductases
  • Aldehyde Reductase
  • Catechol O-Methyltransferase