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 Non-smokers

Autor: Valeria Guidolin, Jing Yang, Viviana Paiano, Silvia Balbo, Stephen S. Hecht, Laura A. Maertens
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Chem Res Toxicol
Popis: 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,N(6)-etheno-dAdo (εdAdo) and 3,N(4)-etheno-dCyd (εdCyd) adducts in oral rinse and cytobrush DNA from smokers and non-smokers 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/10(9) nucleotides, respectively) and non-smokers (1.85 ± 2.08, 5.95 ± 4.23, 7.69 ± 11.7, and 6.07 ± 10.9 adducts/10(9) 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/10(9) nucleotides, respectively) and non-smokers (7.37 ± 5.09, and 16.2 ± 30.2 adducts/10(9) 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.
Databáze: OpenAIRE