Pyridyloxobutylated DNA adducts in oral mucosa of nonsmokers, smokers and snuff dippers in relation to other biomarkers of exposure

1883 Pyridyloxobutylated (POB) DNA adducts releasing 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) have been implicated in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced lung cancer and N’-nitrosonornicotine (NNN) induced esophageal tumors. However, biomonitoring studies of these adducts have not shown the expected specificity for smoking in either lung tissue or esophageal mucosa. NNK and NNN are also implicated in oral cancer of both smokers and snuff dippers. At present, the concept that currently available smokeless tobacco products (SLT) should be used as a substitute for cigarette smoking is controversely discussed. If at all, SLT should have low concentrations of NNN and NNK as is the case of Swedish snus. In the present study, POB DNA adduct were determined in buccal cells from 45 nonsmokers, 24 smokers, and 33 users of Swedish snus. Samples of oral mucosa were collected by Cytobrush Plus® from the left and right cheek, and from the site where snus was normally placed. Subjects filled in a questionnaire on smoking and dietary habits. Saliva and 1-2 mm clippings of the toenails were sampled for estimation of short- and long-term exposure to tobacco alkaloids. HPB-releasing adducts were determined after acid hydrolysis of DNA and derivatization by high-resolution gas chromatography/mass spectrometry with negative chemical ionization. Cotinine and myosmine in saliva and, together with nicotine, in toenails were determined by gas chromatography/mass spectrometry in the EI mode. Highly significant (p