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[Cancer Research 58, 581-584, February 15, 1998]
© 1998 American Association for Cancer Research

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1,N2-Propanodeoxyguanosine Adducts: Potential New Biomarkers of Smoking-induced DNA Damage in Human Oral Tissue1

Raghu G. Nath, Joseph E. Ocando, Joseph B. Guttenplan and Fung-Lung Chung2

American Health Foundation, Division of Carcinogenesis and Molecular Epidemiology, Valhalla, New York 10595 [R. G. N., J. E. O., F-L. C.], and Division of Basic Science, New York University, College of Dentistry and Department of Environmental Medicine, New York University Medical School, New York, New York 10010 [J. B. G.]

Highly DNA-reactive {alpha},ß-unsaturated aldehydes such as acrolein and crotonaldehyde are common environmental pollutants present in cigarette smoke and automobile exhaust and are also released endogenously by lipid peroxidation. Acrolein- and crotonaldehyde-derived 1,N2-propanodeoxyguanosine (AdG and CdG, respectively) have been detected in the tissues of carcinogen-treated rodents and as background lesions in DNA from humans and untreated rodents. To determine whether cigarette smoking increases the levels of AdG and CdG, gingival tissue DNA from 11 smokers (4 males and 7 females; 30–58 years old) and 12 nonsmokers (8 males and 4 females; 21–66 years old) was analyzed using a previously described 32P-postlabeling high-performance liquid chromatography method. The results showed that the mean AdG levels in smokers were significantly higher than those in nonsmokers (1.36 ± 0.90 µmol/mol guanine in smokers versus 0.46 ± 0.26 µmol/mol guanine in nonsmokers; P = 0.003). The mean CdG 1 levels in smokers and nonsmokers were 0.53 ± 0.44 and 0.06 ± 0.07 µmol/mol guanine, respectively, corresponding to an 8.8-fold increase for smokers (P = 0.0015). Similar to CdG 1, levels of CdG 2 were increased 5.5-fold in smokers as compared to nonsmokers, from 0.31 ± 0.40 to 1.72 ± 1.26 µmol/mol guanine (P = 0.0014). Furthermore, the total levels of cyclic adduct (AdG and CdG) in smokers were 4.4-fold greater than those in nonsmokers (P = 0.0003). This study shows the detection of the potentially promutagenic 1,N2-propanoguanine adducts in human oral tissues and demonstrates for the first time an increase of structurally identified adducts in oral tissue DNA by cigarette smoking.

1 Supported by National Cancer Institute Grant CA 43159 and National Institute of Dental Research Grant DE 10549.

2 To whom correspondence should be addressed, at American Health Foundation, Division of Carcinogenesis and Molecular Epidemiology, 1 Dana Road, Valhalla, NY 10595. Phone: (914) 789-7161; Fax: (914) 592-6317; E-mail: ChungAHF.aol.com.

Received 12/ 1/97. Accepted 1/ 2/98.




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