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ToxSci Advance Access published online on August 27, 2003

Toxicological Sciences, doi:10.1093/toxsci/kfg219
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received May 22, 2003; accepted August 11, 2003
© 2003 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 1*, Chia-Liang Hong 1, Chan-Fu Wu 1, and Wei-Loong Chiu 1

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

* To whom correspondence should be addressed. E-mail: chehjc{at}ccunix.ccu.edu.tw.


   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 detection of 3,N4-ethenocytosine ({varepsilon}Cyt) urine samples of two smokers using the isotope dilution gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS) assay (Chen et al., Chem. Res. Toxicol. (2001) 14, 1612-1619). Since smokers are found to have elevated levels of lipid peroxidation and oxidative stress, we thus examine 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 ng/kg/g creatinine versus 0.61 ± 0.90 ng/kg/g creatinine (p = 0.03). Albeit the number of subjects is limited, the results indicate that 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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