Identification and quantification of in vivo metabolites of 9,10-phenanthrenequinone in human urine associated with producing reactive oxygen species

Miki Asahi, Mio Kawai, Takashi Toyama, Yoshito Kumagai, Thanyarat Chuesaard, Ning Tang, Takayuki Kameda, Kazuichi Hayakawa, Akira Toriba

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Polycyclic aromatic hydrocarbon quinones (PAHQs) are components in airborne particulate matter (PM) and generate reactive oxygen species (ROS) in a redox cycling process. 9,10-Phenanthrenequinone (9,10-PQ) is a PAHQ found in diesel exhaust particulates and PM. When inhaled, it produces much more ROS than other PAHQs. We hypothesized that urinary metabolites of 9,10-PQ could serve as biomarkers of PAHQ exposure. Here, we describe methods for pretreating urine samples and analyzing 9,10-PQ metabolites by liquid chromatography with tandem mass spectrometry (LC-MS/MS). In urine from rats intraperitoneally injected with 9,10-PQ, the monoglucuronide of 9,10-dihydroxyphenanthrene (9,10-PQHG) was found to be a major metabolite of 9,10-PQ. 9,10-PQHG was also identified in the urine of a nonoccupationally exposed human by its retention time and MS/MS spectra. Furthermore, the urine contained hardly any free (unmetabolized) 9,10-PQ, but treating it with hydrolytic enzymes released 9,10-PQ from conjugated metabolites such as 9,10-PQHG. The concentrations of 9,10-PQHG in urine samples from nonoccupationally exposed subjects who lived in a suburban area were 2.04-19.08 nmol/mol creatinine. This study is the first to demonstrate the presence of 9,10-PQHG in human urine. Determination of urinary 9,10-PQHG should be useful for determining 9,10-PQ exposure.

Original languageEnglish
Pages (from-to)76-85
Number of pages10
JournalChemical Research in Toxicology
Volume27
Issue number1
DOIs
Publication statusPublished - 2014 Jan 21
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology

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