Quantitation of phenanthrene dihydrodiols in the urine of smokers and non-smokers by gas chromatography-negative ion chemical ionization-tandem mass spectrometry

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Abstract

Polycyclic aromatic hydrocarbons (PAH) are well-established environmental carcinogens likely to be causative agents for some human cancers. Bay-region diol epoxides are ultimate carcinogenic metabolites of multiple PAH. Dihydrodiols are the important intermediate products of this pathway and can be further oxidized to form diol epoxides. We quantified two dihydrodiol metabolites of phenanthrene (Phe), the simplest PAH with a bay-region, in the 6 h urine of smokers (N = 25) and non-smokers (N = 25) using a newly developed and validated analytical method. After hydrolysis by ß-glucuronidase and sulfatase, and solid phase extraction, the sample was silylated and analyzed by gas chromatography-negative ion chemical ionization-tandem mass spectrometry (GC-NICI-MS/MS). Levels (nmol/6h urine) of Phe-1,2-dihydrodiol (Phe-1,2-D) and Phe-3,4-dihydrodiol (Phe-3,4-D) were 2.04 ± 1.52 and 0.51 ± 0.35, respectively, in smokers, significantly higher than those in non-smokers (1.35 ± 1.11 of Phe-1,2-D, p < 0.05; 0.27 ± 0.25 of Phe-3,4-D, p < 0.005). Cigarette smoking also influenced the regioselective metabolism of Phe, presenting as a significant difference in the urinary distribution pattern of Phe-1,2-D and Phe-3,4-D between smokers and non-smokers: the ratio Phe-3,4-D: Phe-1,2-D increased from 0.20 in non-smokers to 0.28 in smokers (p < 0.01), which can be explained by the induction of the phenanthrene metabolizing enzymes CYP1A2 and CYP1B1 by cigarette smoke. The method described here is the first example of facile quantitation of an intact human dihydrodiol metabolite of any PAH with three or more aromatic rings and will be applicable in clinical and molecular epidemiology studies of PAH metabolism and cancer susceptibility.

Original languageEnglish (US)
Article number122023
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1141
DOIs
StatePublished - Mar 15 2020

Bibliographical note

Funding Information:
This study was supported by grants CA-138338 and CA-203851 from the National Cancer Institute and the FDA Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. We thank Bob Carlson for his editorial assistance. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, supported in part by Cancer Center Support Grant CA-77598.

Publisher Copyright:
© 2020 Elsevier B.V.

Keywords

  • Bioactivation
  • Cigarette Smoke
  • Dihydrodiol
  • Phenanthrene

PubMed: MeSH publication types

  • Journal Article

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