Identification and Quantification of in Vivo Metabolites of 9,10-Phenanthrenequinone in Human Urine Associated with Producing Reactive Oxygen Species

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• 作者：Miki Asahi ; Mio Kawai ; Takashi Toyama ; Yoshito Kumagai ; Thanyarat Chuesaard ; Ning Tang ; Takayuki Kameda ; Kazuichi Hayakawa ; Akira Toriba
• 刊名：Chemical Research in Toxicology
• 出版年：2014
• 出版时间：January 21, 2014
• 年：2014
• 卷：27
• 期：1
• 页码：76-85
• 全文大小：370K
• ISSN：1520-5010

文摘

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鈥揗S/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鈥?9.08 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.