Quantitative Liquid Chromatography-Nanoelectrospray Ionization-High-Resolution Tandem Mass Spectrometry Analysis of Acrolein-DNA Adducts and Etheno-DNA Adducts in Oral Cells from Cigarette Smokers and Nonsmokers

Viviana Paiano, Laura Maertens, Valeria Guidolin, Jing Yang, Silvia Balbo, Stephen S. Hecht

Research output: Contribution to journalArticlepeer-review

Abstract

Cigarette smoking is an important source of human exposure to toxicants and carcinogens and contributes significantly to cancer morbidity and mortality worldwide. Acrolein, a widespread environmental pollutant, is present in relatively high amounts in cigarette smoke and can react directly with DNA to form DNA adducts, which serve as important biomarkers for the assessment of exposure to acrolein and its potential role in smoking related cancer. Etheno-DNA adducts are promutagenic DNA lesions that can derive from exogenous chemicals as well as endogenous sources, including lipid peroxidation. In this study, we developed a combined method for the quantitation of (6R/S)-3-(2′-deoxyribos-1′-yl)-5,6,7,8,-tetrahydro-6-hydroxypyrimido[1,2-a]purine-10(3H)-one (α-OH-Acr-dGuo), (8R/S)-3-(2′-deoxyribos-1′-yl)-5,6,7,8,-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10(3H)-one (γ-OH-Acr-dGuo), 1,N6-etheno-dAdo (ϵdAdo), and 3,N4-etheno-dCyd (ϵdCyd) adducts in oral rinse and cytobrush DNA from smokers and nonsmokers by liquid chromatography-nanoelelctrospray ionization-high-resolution tandem mass spectrometry (LC-NSI-HRMS/MS). For oral rinse samples, there was a statistically significant difference between the levels of α-OH-Acr-dGuo, γ-OH-Acr-dGuo, ϵdAdo, and ϵdCyd in smokers (12.1 ± 17.9, 163 ± 227, 182 ± 568, and 194 ± 400 adducts/109 nucleotides, respectively) and nonsmokers (1.85 ± 2.08, 5.95 ± 4.23, 7.69 ± 11.7, and 6.07 ± 10.9 adducts/109 nucleotides, respectively). For cytobrush samples, there was a statistically significant difference between the levels of γ-OH-Acr-dGuo and ϵdAdo in smokers (259 ± 540 and 82.9 ± 271 adducts/109 nucleotides, respectively) and nonsmokers (7.37 ± 5.09 and 16.2 ± 30.2 adducts/109 nucleotides, respectively) but not for α-OH-Acr-dGuo and ϵdCyd. Our results demonstrate that oral mucosa cells are an excellent source of material for evaluating DNA adducts to be used as biomarkers of tobacco smoke exposure and molecular changes potentially related to cancer.

Original languageEnglish (US)
Pages (from-to)2197-2207
Number of pages11
JournalChemical research in toxicology
Volume33
Issue number8
DOIs
StatePublished - Aug 17 2020

Bibliographical note

Funding Information:
This study was supported by Grant P01-CA-138338 from the National Cancer Institute. 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-077598.

PubMed: MeSH publication types

  • Journal Article

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