Abstract 1756: Electronic cigarettes induce DNA damage in the oral epithelium of users

Abstract Background: The use of electronic cigarettes (e-cigs) has skyrocketed among adolescents and young adults. E-cigs are promoted as safer than combustible cigarettes but their long term effects on human health are still unknown. E-cig aerosols contain significantly lower number of chemicals than tobacco smoke, however they also contain known carcinogens, reactive oxygen species (ROS), and unique chemicals poorly studied. In vitro and animal studies revealed that e-cig aerosols increases DNA damage and reduces DNA repair. There have been no studies assessing e-cig-induced DNA damage in human subjects. This reflects, at least in part, technical limitations that make it quite challenging to measure the in vivo steady-state levels of DNA damage, particularly for relatively low levels of genotoxic exposure. Our lab has previously developed and validated a novel quantitative primer anchored DNA damage detection assay (q-PADDA) to quantify in vivo DNA damage. We have also reported that, in an in vitro setting, q-PADDA has high sensitivity to detect e-cig-induced DNA damage. Here, we take advantage of this assay to start assessing the potential long-term impact of e-cig use on human health. Aim: To determine whether e-cig users have higher levels of DNA damage on oral epithelial cells than non-users. Methods: Ethics Committee approval was obtained. Participants were recruited through internet ads, leaflets, flyers and word-of-mouth. After written informed consent, a total of 35 individuals were included in this study: 20 exclusive e-cigarette users and 15 individuals reporting no e-cig or tobacco use. Self-report of tobacco use was biochemically confirmed by salivary cotinine and by measuring exhaled carbon monoxide (CO). Oral mucosa samples were collected by cytobrush and used for DNA extraction and damage quantification. DNA damage was quantified by q-PADDA within p53, the most frequently mutated gene in human cancer. Plasma nicotine levels were analyzed by liquid chromatography-mass spectrometry. Data was analyzed by Student’s t test. Results: The study including participants using high and low voltage e-cig devices. E-cig users (33 ± 8) and non-users (33 ± 7) had similar age distribution. We observed that oral epithelial cells collected from e-cig users have significantly higher levels of DNA damage in both transcribed and non-transcribed DNA strands of the p53gene when compared to never users. Conclusion: Our work is the first study to measure DNA damage in e-cig users. Our study shows for the first time that e-cig users have significant levels of DNA damage in their oral mucosa epithelium. These data has major clinical implications and suggest that e-cig users might have an increased cancer risk. Further studies are urgently needed to expand these kind of studies and to characterize the molecular mechanisms underlying e-cig induced DNA damage which may leads to cancer. Citation Format: Vengatesh Ganapathy, Theodore Wagener, Lurdes Queimado. Electronic cigarettes induce DNA damage in the oral epithelium of users [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1756.