Tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and <i>N</i>’-nitrosonornicotine (NNN) are believed to play a key role in the lung, oral, and esophageal carcinogenesis in smokers. To exert their carcinogenicity, both compounds require metabolic activation by P450 enzymes, leading to the formation of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts. Our recent study demonstrated that the levels of these adducts are significantly higher in oral cells of smokers with head and neck cancer compared to cancer-free smokers. Therefore, inhibition of HPB-releasing adduct formation in smokers could be pursued as a preventive measure to reduce the incidence of tobacco-induced cancers. We applied our recently developed high-resolution mass spectrometry-based method to investigate the effect of 2-phenethyl isothiocyanate (PEITC), a natural chemopreventive agent, on the levels of HPB-releasing DNA adducts in oral cells of smokers. The study participants ingested 40 mg of PEITC or placebo (olive oil) for 5 days in a randomized within-subject cross-over study design, with the two treatments being separated by a washout period. Analysis of oral samples from 22 study participants shows that the average levels of HPB-releasing DNA adducts are lower during PEITC than placebo treatment: 0.15 vs 0.21 pmol/mg DNA, respectively. Analysis of data by the order of treatment (PEITC-placebo or placebo-PEITC) indicates that the decrease of HPB-releasing DNA adducts in oral cells continues after the termination of PEITC treatment. These preliminary findings are consistent with the urinary biomarker data in the same subjects and provide a basis for further investigation of PEITC as an inhibitor of tobacco induced carcinogenesis in smokers. <br/>

Investigation of the effect of 2-phenethyl isothiocyanate (PEITC) on the levels of 4-hydroxy-1-(3-pyridyl)-1-butanone-releasing DNA adducts in oral cells of smokers

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.