Metabolism of an Alkylated Polycyclic Aromatic Hydrocarbon 5-Methylchrysene in Human Hepatoma (HepG2) Cells

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Exposure to polycyclic aromatic hydrocarbons (PAHs) in the food chain is the major human health hazard associated with the Deepwater Horizon oil spill. C1-chrysenes are representative PAHs present in the crude oil and have been detected in contaminated sea food in amounts that exceed their permissible safety thresholds. We describe the metabolism of the most carcinogenic C1-chrysene regioisomer, 5-methylchrysene (5-MC), in human HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. 5-MC-tetraol, a signature metabolite of the diol-epoxide pathway, was identified as reported previously. Novel O-monosulfonated-5-MC-catechol isomers and O-monomethyl-O-monosulfonated-5-MC-catechol were discovered, and evidence for their precursor ortho-quinones was obtained. The identities of O-monosulfonated-5-MC-1,2-catechol, O-monomethyl-O-monosulfonated-5-MC-1,2-catechol, and 5-MC-1,2-dione were validated by comparison to authentic synthesized standards. Dual metabolic activation of 5-MC involving the formation of bis-electrophiles, i.e., a mono-diol-epoxide and a mono-ortho-quinone within the same structure, bis-diol-epoxides, and bis-ortho-quinones is reported for the first time. Evidence was also obtained for minor metabolic conversion of 5-MC to form monohydroxylated-quinones and bis-phenols. The identification of 5-MC-tetraol, O-monosulfonated-5-MC-1,2-catechol, O-monomethyl-O-monosulfonated-5-MC-1,2-catechol, and 5-MC-1,2-dione supports metabolic activation of 5-MC by P450 and AKR isozymes followed by metabolic detoxification of the ortho-quinone through interception of redox cycling by COMT and SULT isozymes. The major metabolites, O-monosulfonated-catechols and tetraols, could be used as biomarkers of human exposure to 5-MC resulting from oil spills.

Original languageEnglish (US)
Pages (from-to)2045-2058
Number of pages14
JournalChemical Research in Toxicology
Volume28
Issue number10
DOIs
StatePublished - Sep 22 2015

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Polycyclic Aromatic Hydrocarbons
Hep G2 Cells
Metabolism
Hepatocellular Carcinoma
Quinones
Epoxy Compounds
Metabolites
Petroleum Pollution
Oil spills
5-methylchrysene
Chrysenes
Isoenzymes
Chemical activation
Catechols
Seafood
Health hazards
Detoxification
Food Chain
Phenols
Petroleum

ASJC Scopus subject areas

  • Toxicology

Cite this

Huang, M., Zhang, L., Mesaros, C., Hackfeld, L. C., Hodge, R. P., Blair, I. A., & Penning, T. M. (2015). Metabolism of an Alkylated Polycyclic Aromatic Hydrocarbon 5-Methylchrysene in Human Hepatoma (HepG2) Cells. Chemical Research in Toxicology, 28(10), 2045-2058. https://doi.org/10.1021/acs.chemrestox.5b00256

Metabolism of an Alkylated Polycyclic Aromatic Hydrocarbon 5-Methylchrysene in Human Hepatoma (HepG2) Cells. / Huang, Meng; Zhang, Li; Mesaros, Clementina; Hackfeld, Linda C.; Hodge, Richard P.; Blair, Ian A.; Penning, Trevor M.

In: Chemical Research in Toxicology, Vol. 28, No. 10, 22.09.2015, p. 2045-2058.

Research output: Contribution to journalArticle

Huang, M, Zhang, L, Mesaros, C, Hackfeld, LC, Hodge, RP, Blair, IA & Penning, TM 2015, 'Metabolism of an Alkylated Polycyclic Aromatic Hydrocarbon 5-Methylchrysene in Human Hepatoma (HepG2) Cells', Chemical Research in Toxicology, vol. 28, no. 10, pp. 2045-2058. https://doi.org/10.1021/acs.chemrestox.5b00256
Huang, Meng ; Zhang, Li ; Mesaros, Clementina ; Hackfeld, Linda C. ; Hodge, Richard P. ; Blair, Ian A. ; Penning, Trevor M. / Metabolism of an Alkylated Polycyclic Aromatic Hydrocarbon 5-Methylchrysene in Human Hepatoma (HepG2) Cells. In: Chemical Research in Toxicology. 2015 ; Vol. 28, No. 10. pp. 2045-2058.
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