DNA damage, DNA repair and carcinogenicity: Tobacco smoke versus electronic cigarette aerosol

Mutat Res Rev Mutat Res. 2022 Jan-Jun;789:108409. doi: 10.1016/j.mrrev.2021.108409. Epub 2021 Dec 20.


The allure of tobacco smoking is linked to the instant gratification provided by inhaled nicotine. Unfortunately, tobacco curing and burning generates many mutagens including more than 70 carcinogens. There are two types of mutagens and carcinogens in tobacco smoke (TS): direct DNA damaging carcinogens and procarcinogens, which require metabolic activation to become DNA damaging. Recent studies provide three new insights on TS-induced DNA damage. First, two major types of TS DNA damage are induced by direct carcinogen aldehydes, cyclic-1,N2-hydroxy-deoxyguanosine (γ-OH-PdG) and α-methyl-1, N2-γ-OH-PdG, rather than by the procarcinogens, polycyclic aromatic hydrocarbons and aromatic amines. Second, TS reduces DNA repair proteins and activity levels. TS aldehydes also prevent procarcinogen activation. Based on these findings, we propose that aldehydes are major sources of TS induce DNA damage and a driving force for carcinogenesis. E-cigarettes (E-cigs) are designed to deliver nicotine in an aerosol state, without burning tobacco. E-cigarette aerosols (ECAs) contain nicotine, propylene glycol and vegetable glycerin. ECAs induce O6-methyl-deoxyguanosines (O6-medG) and cyclic γ-hydroxy-1,N2--propano-dG (γ-OH-PdG) in mouse lung, heart and bladder tissues and causes a reduction of DNA repair proteins and activity in lungs. Nicotine and nicotine-derived nitrosamine ketone (NNK) induce the same types of DNA adducts and cause DNA repair inhibition in human cells. After long-term exposure, ECAs induce lung adenocarcinoma and bladder urothelial hyperplasia in mice. We propose that E-cig nicotine can be nitrosated in mouse and human cells becoming nitrosamines, thereby causing two carcinogenic effects, induction of DNA damage and inhibition of DNA repair, and that ECA is carcinogenic in mice. Thus, this article reviews the newest literature on DNA adducts and DNA repair inhibition induced by nicotine and ECAs in mice and cultured human cells, and provides insights into ECA carcinogenicity in mice.

Keywords: Carcinogenesis; DNA damage; DNA repair; E-cigarette; Tobacco smoke.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aerosols
  • Aldehydes
  • Animals
  • Carcinogenesis / genetics
  • Carcinogens / toxicity
  • DNA Adducts / genetics
  • DNA Damage
  • DNA Repair / genetics
  • Electronic Nicotine Delivery Systems*
  • Humans
  • Mice
  • Mutagens
  • Nicotine / analysis
  • Smoke
  • Tobacco / adverse effects
  • Tobacco Smoke Pollution* / analysis


  • Aerosols
  • Aldehydes
  • Carcinogens
  • DNA Adducts
  • Mutagens
  • Smoke
  • Tobacco Smoke Pollution
  • Nicotine