Abstract 667: Evaluation of toxicant exposure in U.S. smokers after short-term switching to commercial low-nitrosamine cigarettes
Authors: Aleksandar Knezevich, Jian-Min Yuan, Steven Carmella, Dorothy Hatsukami, Stephen S. Hecht, Irina Stepanov
Journal: Cancer Research (2012)

Abstract Mandated reduction of carcinogens and toxicants in cigarette smoke can be required by the U.S. Food and Drug Administration (FDA). Among the initial smoke constituents proposed for regulation are the carcinogenic tobacco-specific nitrosamines (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and Nα-nitrosonornicotine (NNN), which are believed to play an important role in the development of cancers of the lung, pancreas, oral cavity, and esophagus in smokers. Smoking-machine based measurements demonstrate significant variations in TSNA levels both internationally and among currently marketed U.S. brands. However, human smoking patterns are highly complex, and the machine smoking approach does not provide accurate information on actual TSNA intake by individual smokers. Identification of the machine-measured TSNA levels that can result in significant reduction of their current average intake, as determined by changes in biomarker levels in smokers, is critical in informing future FDA policies. In this study, 18 smokers of cigarettes with relatively high machine-measured smoke concentrations of NNK and NNN were asked to switch to Marlboro Virginia Blend (MVB) - cigarettes with the lowest known TSNA levels on the U.S. market. Urinary levels of cotinine, total NNAL, total NNN, and 1-hydroxypyrene (1-HOP) - biomarkers of exposure to nicotine, NNK, NNN, and polycyclic aromatic hydrocarbons (PAH), respectively - were measured at baseline and after one week of smoking MVB. Average(±SD) levels of carcinogen biomarkers at baseline were: total NNAL, 1.0(±0.7) pmol/mg creatinine; total NNN, 0.034(±0.03) pmol/mg creatinine; and 1-HOP, 0.78(±0.6) pmol/mg creatinine. Corresponding levels after switching to MVB were 0.71(±0.5), 0.039(±0.04), and 1.04(±0.7) pmol/mg creatinine, respectively, with the changes in the levels relative to baseline not being statistically significant. Adjustment for nicotine intake revealed a decrease in urinary total NNAL, total NNN, and 1-HOP by 56%, 31%, and 19%, respectively, after switching to MVB compared to baseline. The only statistically significant change was the decrease in total NNAL levels. The lack of significant decrease in exposure to NNN can be explained by the contribution of endogenously formed NNN to the urinary total NNN measured in smokers. The slightly lower levels of pyrene in the smoke of MVB compared to the baseline cigarette brands could have contributed to the modest change in urinary 1-HOP. In summary, our results demonstrate a significant decrease in NNK intake per mg nicotine after short term switching to commercially available low-nitrosamine cigarettes. However, overall exposure to TSNA was greatly influenced by the individual changes in nicotine intake after switching to MVB. Thus, both carcinogen and nicotine levels may need to be modified in order to reach meaningful reductions in carcinogen intake by smokers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 667. doi:1538-7445.AM2012-667