Identification and Characterization of Oxidative Metabolites of 1‑Chloropyrene

Polycyclic aromatic hydrocarbons (PAHs) and chlorinated PAHs (ClPAHs) are ubiquitous contaminants that bind to the aryl hydrocarbon receptor (AhR) and exhibit mutagenic potential. It is difficult to monitor human exposure levels to ClPAHs because the exposure routes are complicated, and environmenta...

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Bibliographic Details
Published in:Chemical research in toxicology 2015-09, Vol.28 (9), p.1728-1736
Main Authors: Kakimoto, Kensaku, Nagayoshi, Haruna, Inazumi, Naoya, Tani, Atsushi, Konishi, Yoshimasa, Kajimura, Keiji, Ohura, Takeshi, Nakano, Takeshi, Tang, Ning, Hayakawa, Kazuichi, Toriba, Akira
Format: Article
Language:English
Subjects:
Chromatography, Liquid
Humans
Ligands
Magnetic Resonance Spectroscopy
Oxidation-Reduction
Pyrenes - metabolism
Pyrenes - urine
Receptors, Aryl Hydrocarbon - metabolism
Tandem Mass Spectrometry
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Summary:Polycyclic aromatic hydrocarbons (PAHs) and chlorinated PAHs (ClPAHs) are ubiquitous contaminants that bind to the aryl hydrocarbon receptor (AhR) and exhibit mutagenic potential. It is difficult to monitor human exposure levels to ClPAHs because the exposure routes are complicated, and environmental concentrations are not always correlated with the levels of PAHs. Urinary PAH metabolites are useful biomarkers for evaluating PAH exposure, and ClPAH metabolites may therefore contribute to the estimation of ClPAH exposure. One of the most abundant ClPAHs present in the environment is 1-chloropyrene (ClPyr), and urinary ClPyr metabolites have the potential to be good biomarkers to evaluate the level of exposure to ClPAHs. Since the metabolic pathways involving ClPAHs are still undetermined, we investigated the effect of human cytochrome P450 enzymes on ClPyr and identified three oxidative metabolites by liquid chromatography–tandem mass spectrometry and nuclear magnetic resonance. We found that ClPyr was metabolized most efficiently by the P450 1A1 enzyme, followed by the 1B1 and 1A2 enzymes. Similar to ClPyr, these metabolites were shown to have agonist activity for the human AhR. We detected these metabolites when ClPyr reacted with a pooled human liver S9 fraction as well as in human urine samples. These results suggest that the metabolites may be used as biomarkers to evaluate the extent of exposure to ClPAHs.
ISSN:0893-228X
1520-5010
DOI:10.1021/acs.chemrestox.5b00173