Identification and quantification of phenanthrene ortho-quinones in human urine and their association with lipid peroxidation

Kai Luo; Steven G. Carmella; Yingchun Zhao; Mei Kuen Tang; Stephen S. Hecht

doi:10.1016/j.envpol.2020.115342

Identification and quantification of phenanthrene ortho-quinones in human urine and their association with lipid peroxidation

Kai Luo, Steven G. Carmella, Yingchun Zhao, Mei Kuen Tang, Stephen S. Hecht

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Abstract

Although human exposure to polycyclic aromatic hydrocarbons (PAH) has been associated with in vivo oxidative damage, and hydroxyPAH metabolites have been used as biomarkers to assess PAH-induced oxidative stress, few studies have looked at the likely causative compounds for oxidative stress in humans - PAH quinones. We developed a method using pre-column derivatization - liquid chromatography-heated electrospray ionization-tandem mass spectrometry (LC-HESI-MS/MS) to analyze ortho-phenanthrene quinones (PheQs) in human urine. 1,2-PheQ and 3,4-PheQ were identified and quantified in 3 mL of human urine; their total concentrations were higher in cigarette smokers (0.79 ± 0.98 nmol/6h urine) than in nonsmokers (0.20 ± 0.98 nmol/6h urine) (p < 0.01). The total of 1,2-PheQ and 3,4-PheQ were more strongly correlated with urinary (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF_2α), a biomarker of lipid peroxidation (R² = 0.53, p < 0.001), than the other phenanthrene metabolites including phenanthrene tetraol (PheT), phenanthrene-1,2-dihydrodiol (1,2-PheD), and total phenanthrene phenols (OHPhe), consistent with the concept that PheQs and likely other PAH quinones play a causal role in the generation of reactive oxygen species (ROS) in humans. Thus, PheQs may be suitable as biomarkers to assess human exposure to oxygenated PAH and the subsequent oxidative damage. This study provides unique support, by analysis of human urinary metabolites, for the PAH quinone mediated oxidative damage hypothesis of PAH carcinogenesis.

Original language	English (US)
Article number	115342
Journal	Environmental Pollution
Volume	266
DOIs	https://doi.org/10.1016/j.envpol.2020.115342
State	Published - Nov 2020

Bibliographical note

Funding Information:
This study was supported by the National Cancer Institute and FDA Center for Tobacco Products [grant numbers CA-138338 and CA-203851 ]. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota , supported in part by a National Cancer Institute Cancer Center Support Grant [grant number CA-077598 ]. 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.

Funding Information:
This study was supported by the National Cancer Institute and FDA Center for Tobacco Products [grant numbers CA-138338 and CA-203851]. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota, supported in part by a National Cancer Institute Cancer Center Support Grant [grant number CA-077598]. 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.

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

8-iso-PGF
Oxidative damage
Phenanthrene quinone
Polycyclic aromatic hydrocarbons

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title = "Identification and quantification of phenanthrene ortho-quinones in human urine and their association with lipid peroxidation",

abstract = "Although human exposure to polycyclic aromatic hydrocarbons (PAH) has been associated with in vivo oxidative damage, and hydroxyPAH metabolites have been used as biomarkers to assess PAH-induced oxidative stress, few studies have looked at the likely causative compounds for oxidative stress in humans - PAH quinones. We developed a method using pre-column derivatization - liquid chromatography-heated electrospray ionization-tandem mass spectrometry (LC-HESI-MS/MS) to analyze ortho-phenanthrene quinones (PheQs) in human urine. 1,2-PheQ and 3,4-PheQ were identified and quantified in 3 mL of human urine; their total concentrations were higher in cigarette smokers (0.79 ± 0.98 nmol/6h urine) than in nonsmokers (0.20 ± 0.98 nmol/6h urine) (p < 0.01). The total of 1,2-PheQ and 3,4-PheQ were more strongly correlated with urinary (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), a biomarker of lipid peroxidation (R2 = 0.53, p < 0.001), than the other phenanthrene metabolites including phenanthrene tetraol (PheT), phenanthrene-1,2-dihydrodiol (1,2-PheD), and total phenanthrene phenols (OHPhe), consistent with the concept that PheQs and likely other PAH quinones play a causal role in the generation of reactive oxygen species (ROS) in humans. Thus, PheQs may be suitable as biomarkers to assess human exposure to oxygenated PAH and the subsequent oxidative damage. This study provides unique support, by analysis of human urinary metabolites, for the PAH quinone mediated oxidative damage hypothesis of PAH carcinogenesis.",

keywords = "8-iso-PGF, Oxidative damage, Phenanthrene quinone, Polycyclic aromatic hydrocarbons",

author = "Kai Luo and Carmella, {Steven G.} and Yingchun Zhao and Tang, {Mei Kuen} and Hecht, {Stephen S.}",

note = "Funding Information: This study was supported by the National Cancer Institute and FDA Center for Tobacco Products [grant numbers CA-138338 and CA-203851 ]. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota , supported in part by a National Cancer Institute Cancer Center Support Grant [grant number CA-077598 ]. 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. Funding Information: This study was supported by the National Cancer Institute and FDA Center for Tobacco Products [grant numbers CA-138338 and CA-203851]. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota, supported in part by a National Cancer Institute Cancer Center Support Grant [grant number CA-077598]. 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. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

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doi = "10.1016/j.envpol.2020.115342",

language = "English (US)",

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AU - Luo, Kai

AU - Carmella, Steven G.

AU - Zhao, Yingchun

AU - Tang, Mei Kuen

AU - Hecht, Stephen S.

N1 - Funding Information: This study was supported by the National Cancer Institute and FDA Center for Tobacco Products [grant numbers CA-138338 and CA-203851 ]. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota , supported in part by a National Cancer Institute Cancer Center Support Grant [grant number CA-077598 ]. 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. Funding Information: This study was supported by the National Cancer Institute and FDA Center for Tobacco Products [grant numbers CA-138338 and CA-203851]. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota, supported in part by a National Cancer Institute Cancer Center Support Grant [grant number CA-077598]. 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. Publisher Copyright: © 2020 Elsevier Ltd

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N2 - Although human exposure to polycyclic aromatic hydrocarbons (PAH) has been associated with in vivo oxidative damage, and hydroxyPAH metabolites have been used as biomarkers to assess PAH-induced oxidative stress, few studies have looked at the likely causative compounds for oxidative stress in humans - PAH quinones. We developed a method using pre-column derivatization - liquid chromatography-heated electrospray ionization-tandem mass spectrometry (LC-HESI-MS/MS) to analyze ortho-phenanthrene quinones (PheQs) in human urine. 1,2-PheQ and 3,4-PheQ were identified and quantified in 3 mL of human urine; their total concentrations were higher in cigarette smokers (0.79 ± 0.98 nmol/6h urine) than in nonsmokers (0.20 ± 0.98 nmol/6h urine) (p < 0.01). The total of 1,2-PheQ and 3,4-PheQ were more strongly correlated with urinary (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), a biomarker of lipid peroxidation (R2 = 0.53, p < 0.001), than the other phenanthrene metabolites including phenanthrene tetraol (PheT), phenanthrene-1,2-dihydrodiol (1,2-PheD), and total phenanthrene phenols (OHPhe), consistent with the concept that PheQs and likely other PAH quinones play a causal role in the generation of reactive oxygen species (ROS) in humans. Thus, PheQs may be suitable as biomarkers to assess human exposure to oxygenated PAH and the subsequent oxidative damage. This study provides unique support, by analysis of human urinary metabolites, for the PAH quinone mediated oxidative damage hypothesis of PAH carcinogenesis.

AB - Although human exposure to polycyclic aromatic hydrocarbons (PAH) has been associated with in vivo oxidative damage, and hydroxyPAH metabolites have been used as biomarkers to assess PAH-induced oxidative stress, few studies have looked at the likely causative compounds for oxidative stress in humans - PAH quinones. We developed a method using pre-column derivatization - liquid chromatography-heated electrospray ionization-tandem mass spectrometry (LC-HESI-MS/MS) to analyze ortho-phenanthrene quinones (PheQs) in human urine. 1,2-PheQ and 3,4-PheQ were identified and quantified in 3 mL of human urine; their total concentrations were higher in cigarette smokers (0.79 ± 0.98 nmol/6h urine) than in nonsmokers (0.20 ± 0.98 nmol/6h urine) (p < 0.01). The total of 1,2-PheQ and 3,4-PheQ were more strongly correlated with urinary (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), a biomarker of lipid peroxidation (R2 = 0.53, p < 0.001), than the other phenanthrene metabolites including phenanthrene tetraol (PheT), phenanthrene-1,2-dihydrodiol (1,2-PheD), and total phenanthrene phenols (OHPhe), consistent with the concept that PheQs and likely other PAH quinones play a causal role in the generation of reactive oxygen species (ROS) in humans. Thus, PheQs may be suitable as biomarkers to assess human exposure to oxygenated PAH and the subsequent oxidative damage. This study provides unique support, by analysis of human urinary metabolites, for the PAH quinone mediated oxidative damage hypothesis of PAH carcinogenesis.

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KW - Oxidative damage

KW - Phenanthrene quinone

KW - Polycyclic aromatic hydrocarbons

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Identification and quantification of phenanthrene ortho-quinones in human urine and their association with lipid peroxidation

Abstract

Bibliographical note

Keywords

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