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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1093-1101
Number of pages9
JournalChemical Research in Toxicology
Volume30
Issue number4
DOIs
StatePublished - Apr 17 2017

Fingerprint

Petroleum Pollution
Polycyclic Aromatic Hydrocarbons
Oil spills
Hep G2 Cells
Hepatocellular Carcinoma
Chemical activation
Metabolites
Metabolism
Isoenzymes
Phenanthrenes
Catechols
Sulfotransferases
Catechol O-Methyltransferase
Seafood
Quinones
Glucuronosyltransferase
Health hazards
Detoxification
Food Chain
Metabolic Activation

ASJC Scopus subject areas

  • Toxicology

Cite this

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

In: Chemical Research in Toxicology, Vol. 30, No. 4, 17.04.2017, p. 1093-1101.

Research output: Contribution to journalArticle

Huang, Meng ; Mesaros, Clementina ; Hackfeld, Linda C. ; Hodge, Richard P. ; Zang, Tianzhu ; Blair, Ian A. ; Penning, Trevor M. / 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. In: Chemical Research in Toxicology. 2017 ; Vol. 30, No. 4. pp. 1093-1101.
@article{2ec2b1b9a6da44a79b0c6ac911c14952,
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.",
author = "Meng Huang and Clementina Mesaros and Hackfeld, {Linda C.} and Hodge, {Richard P.} and Tianzhu Zang and Blair, {Ian A.} and Penning, {Trevor M.}",
year = "2017",
month = "4",
day = "17",
doi = "10.1021/acs.chemrestox.6b00457",
language = "English (US)",
volume = "30",
pages = "1093--1101",
journal = "Chemical Research in Toxicology",
issn = "0893-228X",
publisher = "American Chemical Society",
number = "4",

}

TY - JOUR

T1 - 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

AU - Huang, Meng

AU - Mesaros, Clementina

AU - Hackfeld, Linda C.

AU - Hodge, Richard P.

AU - Zang, Tianzhu

AU - Blair, Ian A.

AU - Penning, Trevor M.

PY - 2017/4/17

Y1 - 2017/4/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85018511605&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018511605&partnerID=8YFLogxK

U2 - 10.1021/acs.chemrestox.6b00457

DO - 10.1021/acs.chemrestox.6b00457

M3 - Article

VL - 30

SP - 1093

EP - 1101

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

SN - 0893-228X

IS - 4

ER -