Open AccessQuantitative 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
Author(s) -
Viviana Paiano,
Laura A. Maertens,
Valeria Guidolin,
Jing Yang,
Silvia Balbo,
Stephen S. Hecht
Publication year - 2020
Publication title -
chemical research in toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.031
H-Index - 156
eISSN - 1520-5010
pISSN - 0893-228X
DOI - 10.1021/acs.chemrestox.0c00223
Subject(s) - chemistry , adduct , acrolein , carcinogen , dna , tandem mass spectrometry , dna adduct , nucleotide , deoxyguanosine , chromatography , mass spectrometry , purine , biochemistry , organic chemistry , enzyme , gene , catalysis
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 (6 R / S )-3-(2'-deoxyribos-1'-yl)-5,6,7,8,-tetrahydro-6-hydroxypyrimido[1,2- a ]purine-10(3 H )-one (α-OH-Acr-dGuo), (8 R / S )-3-(2'-deoxyribos-1'-yl)-5,6,7,8,-tetrahydro-8-hydroxypyrimido[1,2- a ]purine-10(3 H )-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 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/10 9 nucleotides, respectively) and nonsmokers (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 nonsmokers (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.