title: Identification and characterization of oxidative metabolites of 1-chloropyrene.
abstract: 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.
authors.affiliation: Osaka Prefectural Institute of Public Health , 1-3-69 Nakamichi, Higashinari-ku, Osaka 537-0025, Japan.|Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University , Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Kakimoto
authors.affiliation: Osaka Prefectural Institute of Public Health , 1-3-69 Nakamichi, Higashinari-ku, Osaka 537-0025, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Nagayoshi
authors.affiliation: Technical Support Division, Graduate School of Science, Osaka University , 1-1, Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Inazumi
authors.affiliation: Department of Earth and Space Science, Graduate School of Science, Osaka University , 1-1, Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tani
authors.affiliation: Osaka Prefectural Institute of Public Health , 1-3-69 Nakamichi, Higashinari-ku, Osaka 537-0025, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Konishi
authors.affiliation: Osaka Prefectural Institute of Public Health , 1-3-69 Nakamichi, Higashinari-ku, Osaka 537-0025, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Kajimura
authors.affiliation: Department of Environmental Bioscience, Faculty of Agriculture, Meijo University , 1-501, Shiogamaguchi, Tenpaku-ku, Nagoya 468-8502, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ohura
authors.affiliation: Research Center for Environmental Preservation, Osaka University , 2-4, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University , Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
authors.forename: Ning
authors.initials: N
authors.lastname: Tang
authors.affiliation: Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University , Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University , Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Toriba
mesh_terms: D002853:Chromatography, Liquid; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D011721:Pyrenes / Q000378:metabolism* / Q000652:urine; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D008024:Ligands; D011721:Pyrenes; D018336:Receptors, Aryl Hydrocarbon; C040345:1-chloropyrene