Genotoxic and mutagenic effects of combinations of e-cigarettes and tobacco carcinogens in mouse oral tissues

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This is project is designed to determine whether the use of e-cigarettes (e-cigs) increases the risk for cancer of the oral cavity, especially when combined with tobacco smoke carcinogens. The proposed research will serve as a murine model for users of cigarettes and e-cigs (dual users). As e-cigs have only become popular wi t h i n the last decade and carcinogenesis occurs over decades, there has not been sufficient time for any epidemiological evidence one way or another. Yet e-cigs are currently being used by millions of individuals, and many of the same individuals are also tobacco smokers. In addition, others who are ex-smokers may already harbor precancer or cancer cells in the mouth, and other organs. The proposed research will investigate the effects of e-cig aerosol, tobacco carcinogens and their combinations on several outcomes relevant to carcinogenesis. . A nicotine-only control will be included. The outcomes consist of DNA damage, mutagenesis and changes in expression of critical genes and pathways in drug metabolism and the cell cycle. The use of the combination is to investigate possible cocarcinogenic or promoting effects of E-cigs. The oral cavity is a major site of exposure to e-cigs and there have been few if any reports on the potential carcinogenic effects of e-cig exposure on these sites. The results of this study are likely important and timely, as the experiments on the potential carcinogenic effects of the e-cigs cannot be studied in humans, yet the public is increasingly using e- cigs.