Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage

• Published in: PloS one 2017-05, Vol.12 (5), p.e0177780-e0177780
• Main Authors: Ganapathy, Vengatesh, Manyanga, Jimmy, Brame, Lacy, McGuire, Dehra, Sadhasivam, Balaji, Floyd, Evan, Rubenstein, David A, Ramachandran, Ilangovan, Wagener, Theodore, Queimado, Lurdes
• Format: Article
• Language: English
• Subjects: 8-Hydroxyguanine; Aerosol concentrations; Aerosols; Analysis; Antioxidants; Antioxidants - metabolism; Biology and life sciences; Cancer; Carcinogens; Cell Line; Cigarettes; Damage detection; Deoxyribonucleic acid; DNA; DNA Damage; DNA glycosylase; DNA repair; Dose-Response Relationship, Drug; Electronic cigarettes; Electronic Nicotine Delivery Systems - adverse effects; Enzyme-linked immunosorbent assay; Epithelial cells; Exposure; Federal regulation; Gene expression; Genotoxicity; Health aspects; Health risks; Health sciences; Humans; Measurement methods; Medicine and Health Sciences; mRNA; Mutagenesis; Nicotine; OGG1 protein; Otolaryngology; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - genetics; Oxygen; Pediatrics; Physical Sciences; Polymerase chain reaction; Public health; Reactive oxygen species; Research and analysis methods; Risk factors; Salmonella; Smoke; Smoke - adverse effects; Smoking cessation; Studies; Time Factors; Tobacco; Tobacco smoke; Toxicants; Toxicity; Toxicology; VOCs; Volatile organic compounds
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0177780

Electronic cigarette (EC) aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs. The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells. Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA) and 8-oxo-dG ELISA assay. Cell viability, reactive oxygen species (ROS) and total antioxidant capacity (TAC) were measured using standard methods. mRNA and protein expression were evaluated by RT-PCR and western blot, respectively. EC aerosol extracts induced DNA damage in a dose-dependent manner, but independently of nicotine concentration. Overall, EC aerosol extracts induced significantly less DNA damage than mainstream smoke extracts, as measured by q-PADDA. However, the levels of oxidative DNA damage, as indicated by the presence of 8-oxo-dG, a highly mutagenic DNA lesion, were similar or slightly higher after exposure to EC aerosol compared to mainstream smoke extracts. Mechanistically, while exposure to EC extracts significantly increased ROS, it decreased TAC as well as the expression of 8-oxoguanine DNA glycosylase (OGG1), an enzyme essential for the removal of oxidative DNA damage. Exposure to EC aerosol extracts suppressed the cellular antioxidant defenses and led to significant DNA damage. These findings emphasize the urgent need to investigate the potential long-term cancer risk of exposure to EC aerosol for vapers and the general public.