The number of people who use e-cigarettes is rapidly rising, so it is increasingly important to understand whether e-cigarette aerosol may lead to lung cancer. E-cigarettes contain nicotine, and e-cigarette aerosol does not involve burning tobacco leaves. As a result, e-cigarettes are promoted as non-carcinogenic. As a first step to test the cancer-causing potential of e-cigarette smoke, we measured DNA damage induced by nicotine in human lung cells and the lungs of mice exposed to the e-cigarette smoke. We have found that nicotine and e-cigarette aerosol induce not only DNA damage but also reduce DNA repair, and enhances the susceptibility to genetic mutation and transformation into tumors. We will further test e-cigarette aerosol in mouse models and analyze the changes in DNA and the effects on DNA repair. Establishing the cancer-causing potential of e-cigarette aerosol and understanding its mechanisms will dispel the claim that e-cigarettes are safe and might discourage their use.