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ToxSci Advance Access originally published online on August 27, 2003
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Toxicological Sciences 76, 321-327 (2003)
Copyright © 2003 by the Society of Toxicology


GENETIC TOXICOLOGY

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

Hauh-Jyun Candy Chen*, Chia-Liang Hong, Chan-Fu Wu and Wei-Loong Chiu

Department of Chemistry and Biochemistry, National Chung Cheng University, 160 San-Hsing, Ming-Hsiung, Chia-Yi 62142, Taiwan

ABSTRACT

Etheno DNA adducts are DNA damages derived from exogenous 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 ({varepsilon}Cyt) in the urine samples of two smokers using the isotope dilution gas chromatography/negative ion chemical ionization/mass spectrometry (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 association between urinary {varepsilon}Cyt levels with cigarette smoking. Among the 23 samples analyzed, the average concentration of urinary {varepsilon}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 {varepsilon}Cyt in human urine may provide a useful noninvasive biomarker for oxidative DNA damage and cancer chemoprevention studies.

Key Words: biomarker; cigarette smoking; 3,N4-ethenocytosine; gas chromatography; mass spectrometry; urine.


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