LAUSR

Significance Electronic-cigarette smoke (ECS) is designed to deliver nicotine, and its use is gaining popularity. Previously, we found that ECS induces DNA damage and inhibits DNA repair in the mouse lungs and bladder urothelium. Nicotine induces the same types of DNA adducts and has a similar effect on DNA repair inhibition in human cells. Nicotine also enhances human cells’ mutation and tumorigenic transformation susceptibility. Our current results show that ECS-exposed mice developed lung adenocarcinoma and bladder urothelial hyperplasia, indicating that ECS is a lung carcinogen and a potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, the threat ECS poses to humans is not yet known and warrants in-depth investigation. Electronic-cigarettes (E-cigs) are marketed as a safe alternative to tobacco to deliver the stimulant nicotine, and their use is gaining in popularity, particularly among the younger population. We recently showed that mice exposed to short-term (12 wk) E-cig smoke (ECS) sustained extensive DNA damage in lungs, heart, and bladder mucosa and diminished DNA repair in lungs. Nicotine and its nitrosation product, nicotine-derived nitrosamine ketone, cause the same deleterious effects in human lung epithelial and bladder urothelial cells. These findings raise the possibility that ECS is a lung and bladder carcinogen in addition to nicotine. Given the fact that E-cig use has become popular in the past decade, epidemiological data on the relationship between ECS and human cancer may not be known for a decade to come. In this study, the carcinogenicity of ECS was tested in mice. We found that mice exposed to ECS for 54 wk developed lung adenocarcinomas (9 of 40 mice, 22.5%) and bladder urothelial hyperplasia (23 of 40 mice, 57.5%). These lesions were extremely rare in mice exposed to vehicle control or filtered air. Current observations that ECS induces lung adenocarcinomas and bladder urothelial hyperplasia, combined with our previous findings that ECS induces DNA damage in the lungs and bladder and inhibits DNA repair in lung tissues, implicate ECS as a lung and potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, whether ECS poses any threat to humans is not yet known and warrants careful investigation.