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 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.
