Potential Metabolic Activation of Representative Alkylated Polycyclic Aromatic Hydrocarbons 1-Methylphenanthrene and 9-Ethylphenanthrene Associated with the Deepwater Horizon Oil Spill in Human Hepatoma (HepG2) Cells

Meng Huang, Clementina Mesaros, Linda C. Hackfeld, Richard P. Hodge, Ian A. Blair, Trevor M. Penning

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Exposure to petrogenic polycyclic aromatic hydrocarbons (PPAHs) is the major human health hazard associated with the Deepwater Horizon oil spill. Alkylated phenanthrenes are the most abundant PPAHs present in the crude oil and could contaminate the food chain. We describe the metabolism of a C1-phenanthrene regioisomer 1-methylphenanthrene (1-MP) and a C2-phenanthrene regioisomer 9-ethylphenanthrene (9-EP) in human HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. Side chain hydroxylation of 1-MP and 9-EP was observed as the major metabolic pathway. The formation of 1-(hydroxymethyl)-phenanthrene was confirmed by reference to an authentic synthetic standard. However, formation of the bioactivated sulfate was not detected. Tetraols were also identified as signature metabolites of 1-MP and 9-EP, indicating that metabolic activation occurred via the diol-epoxide pathway. O-Monosulfonated-catechols were discovered as signature metabolites of the o-quinone pathway of metabolic activation of 1-MP and 9-EP, respectively. The identification of O-monosulfonated-catechols supports the metabolic activation of 1-MP and 9-EP by P450 and AKR isozymes followed by metabolic detoxification of the o-quinone through interception of redox cycling by phase II isozymes. The signature metabolites identified could be used as biomarkers of human exposure to 1-MP and 9-EP resulting from oil spills.

Original languageEnglish (US)
Pages (from-to)2140-2150
Number of pages11
JournalChemical Research in Toxicology
Volume30
Issue number12
DOIs
StatePublished - Dec 18 2017

Fingerprint

Petroleum Pollution
Polycyclic Aromatic Hydrocarbons
Oil spills
Hep G2 Cells
Hepatocellular Carcinoma
Chemical activation
Metabolites
Catechols
Isoenzymes
Phenanthrenes
Health hazards
Detoxification
Hydroxylation
Food Chain
Epoxy Compounds
Petroleum
Biomarkers
Metabolic Networks and Pathways
Metabolism
Sulfates

ASJC Scopus subject areas

  • Toxicology

Cite this

Potential Metabolic Activation of Representative Alkylated Polycyclic Aromatic Hydrocarbons 1-Methylphenanthrene and 9-Ethylphenanthrene Associated with the Deepwater Horizon Oil Spill in Human Hepatoma (HepG2) Cells. / Huang, Meng; Mesaros, Clementina; Hackfeld, Linda C.; Hodge, Richard P.; Blair, Ian A.; Penning, Trevor M.

In: Chemical Research in Toxicology, Vol. 30, No. 12, 18.12.2017, p. 2140-2150.

Research output: Contribution to journalArticle

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abstract = "Exposure to petrogenic polycyclic aromatic hydrocarbons (PPAHs) is the major human health hazard associated with the Deepwater Horizon oil spill. Alkylated phenanthrenes are the most abundant PPAHs present in the crude oil and could contaminate the food chain. We describe the metabolism of a C1-phenanthrene regioisomer 1-methylphenanthrene (1-MP) and a C2-phenanthrene regioisomer 9-ethylphenanthrene (9-EP) in human HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. Side chain hydroxylation of 1-MP and 9-EP was observed as the major metabolic pathway. The formation of 1-(hydroxymethyl)-phenanthrene was confirmed by reference to an authentic synthetic standard. However, formation of the bioactivated sulfate was not detected. Tetraols were also identified as signature metabolites of 1-MP and 9-EP, indicating that metabolic activation occurred via the diol-epoxide pathway. O-Monosulfonated-catechols were discovered as signature metabolites of the o-quinone pathway of metabolic activation of 1-MP and 9-EP, respectively. The identification of O-monosulfonated-catechols supports the metabolic activation of 1-MP and 9-EP by P450 and AKR isozymes followed by metabolic detoxification of the o-quinone through interception of redox cycling by phase II isozymes. The signature metabolites identified could be used as biomarkers of human exposure to 1-MP and 9-EP resulting from oil spills.",
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AB - Exposure to petrogenic polycyclic aromatic hydrocarbons (PPAHs) is the major human health hazard associated with the Deepwater Horizon oil spill. Alkylated phenanthrenes are the most abundant PPAHs present in the crude oil and could contaminate the food chain. We describe the metabolism of a C1-phenanthrene regioisomer 1-methylphenanthrene (1-MP) and a C2-phenanthrene regioisomer 9-ethylphenanthrene (9-EP) in human HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. Side chain hydroxylation of 1-MP and 9-EP was observed as the major metabolic pathway. The formation of 1-(hydroxymethyl)-phenanthrene was confirmed by reference to an authentic synthetic standard. However, formation of the bioactivated sulfate was not detected. Tetraols were also identified as signature metabolites of 1-MP and 9-EP, indicating that metabolic activation occurred via the diol-epoxide pathway. O-Monosulfonated-catechols were discovered as signature metabolites of the o-quinone pathway of metabolic activation of 1-MP and 9-EP, respectively. The identification of O-monosulfonated-catechols supports the metabolic activation of 1-MP and 9-EP by P450 and AKR isozymes followed by metabolic detoxification of the o-quinone through interception of redox cycling by phase II isozymes. The signature metabolites identified could be used as biomarkers of human exposure to 1-MP and 9-EP resulting from oil spills.

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