Identification and Quantification of 1-Nitropyrene Metabolites in Human Urine as a Proposed Biomarker for Exposure to Diesel Exhaust

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• 作者：Akira Toriba ; Hitomi Kitaoka ; Russell L. Dills ; Satoko Mizukami ; Kaori Tanabe ; Naoki Takeuchi ; Mariko Ueno ; Takayuki Kameda ; Ning Tang ; Kazuichi Hayakawa ; Christopher D. Simpson
• 刊名：Chemical Research in Toxicology
• 出版年：2007
• 出版时间：July 2007
• 年：2007
• 卷：20
• 期：7
• 页码：999 - 1007
• 全文大小：125K
• 年卷期：v.20,no.7(July 2007)
• ISSN：1520-5010

文摘

1-Nitropyrene (1-NP) is one of the most abundant nitrated polycyclic aromatic hydrocarbons (NPAHs)in diesel exhaust particulate matter (DEP) and is a main contributor of direct-acting mutagenicity inDEP. Therefore, the metabolites of 1-NP are expected to be a biomarker for assessment of exposure toDEP. In this study, a highly specific and sensitive analytical method using liquid chromatography withtandem mass spectrometry (LC-MS/MS) was developed to determine urinary 1-NP metabolites. Afterenzymatic hydrolysis of the conjugated metabolites, the analytes were selectively extracted from theurine matrix with blue rayon. The eluate from the rayon was further purified on an acidic alumina cartridge.Hydroxy-N-acetyl- 1-aminopyrenes (6- and 8-OHNAAP) and hydroxy-1-nitropyrenes (3-, 6-, and 8-OHNP)in human urine were identified by their retention times and MS/MS spectra and quantified by usingdeuterated internal standards. 1-NP metabolites were quantified in urine from all healthy, nonoccupationallyexposed subjects. 6-OHNAAP, 8-OHNAAP, 6-OHNP, and 8-OHNP (means of 117, 109, 203, and 137pmol/mol creatinine, respectively) were the most abundant isomers in human urine. This report is thefirst to demonstrate the presence of OHNAAPs and OHNPs in human urine, in agreement with previousin vivo and in vitro studies that predicted that these metabolites should be excreted into human urine.This method for determining urinary 1-NP metabolites should be useful for the surveillance of exposureto NPAHs and DEP and will facilitate the study of cancer risk associated with these exposures.