Effect of Cigarette Smoking on Urinary 3,N4-Ethenocytosine Levels Measured by Gas Chromatography/Mass Spectrometry

Etheno DNA adducts are DNA damages derived from exoge-nous carcinogens as well as endogenous lipid peroxidation and oxidative stress. Elevated levels of etheno DNA adducts were found in cancer-prone tissues and blood samples, suggesting that these promutagenic lesions correlate with risk of cancers. We previously reported the detection of 3,N4-ethenocytosine (Cyt) in the urine samples of two smokers using the isotope dilution gas chromatography/negative ion chemical ionization/mass spectrom-etry (GC/NICI/MS) assay (Chen et al., 2001, Chem. Res. Toxicol. 14, 1612–1619). Since smokers are found to have elevated levels of lipid peroxidation and oxidative stress, we examined the associa-tion between urinary Cyt levels with cigarette smoking. Among the 23 samples analyzed, the average concentration of urinary Cyt in smokers was significantly higher than that of nonsmokers, 2.65 4.0 versus 0.61 0.90 ng/kg/g creatinine (p 0.03). Albeit the number of subjects is limited, the results indicate that the measurement of Cyt in human urine may provide a useful non-invasive biomarker for oxidative DNA damage and cancer che-moprevention studies. Key Words: biomarker; cigarette smoking; 3,N4-ethenocytosine; gas chromatography; mass spectrometry; urin