Dataset Information

Analysis of Acrolein-Derived 1, N2-Propanodeoxyguanosine Adducts in Human Lung DNA from Smokers and Nonsmokers.

ABSTRACT: Acrolein, the simplest ?,?-unsaturated aldehyde, is present in relatively large quantities in cigarette smoke, and several studies have raised the possibility of it being a major etiological agent for smoking-related lung cancer. Acrolein reacts directly with DNA to form primarily Acr-dGuo adducts, which serve as important biomarkers for the assessment of exposure to acrolein and its potential role in smoking-related lung cancer. In this study, we developed an ultrasensitive and low-artifact method using liquid chromatography-nanoelectrospray ionization-high-resolution tandem mass spectrometry to quantitate Acr-dGuo adducts in normal lung tissue DNA obtained at surgery from lung cancer patients who never smoked and from those who continued smoking until surgery, as confirmed by urinary total cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. This provides a direct comparison of Acr-dGuo levels in human lung tissue as a result of cigarette smoking versus other etiological causes. There was no significant difference between the total Acr-dGuo levels in smokers (28.5 ± 14.9 adducts/109 nucleotides) and nonsmokers (25.0 ± 10.7 adducts/109 nucleotides), suggesting rapid removal of acrolein by glutathione conjugation and other detoxification mechanisms. Our results do not support the hypothesis that acrolein is a major etiological agent for cigarette smoking-related DNA damage.

SUBMITTER: Yang J

PROVIDER: S-EPMC6644703 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Analysis of Acrolein-Derived 1, N<sup>2</sup>-Propanodeoxyguanosine Adducts in Human Lung DNA from Smokers and Nonsmokers.

Yang Jing J Balbo Silvia S Villalta Peter W PW Hecht Stephen S SS

Chemical research in toxicology 20190130 2

Acrolein, the simplest α,β-unsaturated aldehyde, is present in relatively large quantities in cigarette smoke, and several studies have raised the possibility of it being a major etiological agent for smoking-related lung cancer. Acrolein reacts directly with DNA to form primarily Acr-dGuo adducts, which serve as important biomarkers for the assessment of exposure to acrolein and its potential role in smoking-related lung cancer. In this study, we developed an ultrasensitive and low-artifact met ...[more]

PMID: 30644728

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Project description: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.

Dataset Information

Analysis of Acrolein-Derived 1, N2-Propanodeoxyguanosine Adducts in Human Lung DNA from Smokers and Nonsmokers.

Publications

Analysis of Acrolein-Derived 1, N<sup>2</sup>-Propanodeoxyguanosine Adducts in Human Lung DNA from Smokers and Nonsmokers.

Similar Datasets

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