Evaluation of Product and Physiological Variables Influencing Smokeless Tobacco ToxicityVariables Influencing Smokeless Tobacco Toxicity
Principal Investigator: Huizhong Chen/Maocheng (Tony) Yeng & Patricia Richter
Funding Mechanism: JV
ID number: E0747201
Award Date: 4/20/2012
Institution: National Center for Toxicological Research
Smokeless tobacco products contain more than 30 carcinogens, including tobacco-specific N-nitrosamines (TSNAs), polycyclic aromatic hydrocarbons (PAHs), and radioactive metals that contribute to numerous health problems including cancer and cardiovascular disease. Much of the risk associated with oral cancer from smokeless tobacco use has been attributed to TSNAs. The physiologic and product variables of smokeless tobacco products can significantly affect TSNA levels and their bioavailability, leading to different degrees of product toxicity. A combination of factors -- such as pH, tobacco type, nitrate fertilization/uptake, curing, fermentation, and storage conditions -- can contribute to extremely high TSNA concentrations. Furthermore, the genotoxicity of smokeless tobacco products may increase or decrease through metabolism by oral bacteria; the potential roles that oral bacteria play in converting smokeless tobacco ingredients to more or less genotoxic and carcinogenetic substances have not been well studied. This study will evaluate smokeless tobacco genotoxicity levels due to microbial metabolism, the effects of physiological variables on harmful and potentially harmful constituent (HPHC) bioactivation, and the effects of smokeless tobacco on the microbial ecology of the oral cavity. Study aims are: (1) to identify physiological and product variables that influence smokeless tobacco toxicity and metabolic activation of TSNAs, PAHs, and other select HPHCs by oral bacteria; and (2) to conduct a pilot study to investigate how smokeless tobacco genotoxicity is affected by metabolism by oral bacteria and to determine the effect of smokeless tobacco on the ecological balance of human oral microbiota.