Evaluation and comparison of DNA alkylation and oxidative damage in e-cigarette and heated tobacco users

Objectives: This study, aimed to determine and compare DNA damage in e-cigarette and HTP (IQOS) users by assessing DNA-adducts, which are biomarkers of various DNA alkylation and oxidation. Methods: For the evaluation of DNA alkylation, N-3-Ethyladenine (N-3-EtA) and N-3-Methyladenine (N-3-MeA) adducts were used. DNA oxidation was assessed using, 8-hydroxy-2'-deoxyguanosine(8-OHdG). The urinary cotinine, N-3-MeA, N-3-EtA, and 8-OHdG concentrations of the cigarette smokers (n:39), e-cigarette users (n:28), IQOS users (n:20), passive smokers (n:32), and nonsmokers(n:41) who lived Ankara, Turkiye were determined using, liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: In light of the detected 8-OHdG levels, e-cigarette (3.19 ng/g creatinine) and IQOS (4.38 ng/g creatinine) users had higher oxidative DNA damage than healthy nonsmokers (2.51 ng/g creatinine). Alkylated DNA-adducts were identified in the urine of e-cigarette (N-3-MeA: 3.92 ng/g creatinine; N-3-EtA: 0.23 ng/g creatinine) and IQOS (N-3-MeA: 7.54 ng/g creatinine; N-3-EtA: 0.29 ng/g creatinine) users. In the generation of N-3-MeA adducts, a significant difference was found between IQOS users and e-cigarette users (p < 0.05). Also, DNA alkylation in flavored e-cigarette users (N-3-MeA: 4.51 ng/g creatinine; N-3-EtA: 0.27 ng/g creatinine) was higher than in non-flavored e-cigarette users (N-3-MeA: 2.27 ng/g creatinine; N-3-EtA: 0.06 ng/g creatinine). The highest cotinine levels were found in cigarette smokers (16.1316 ng/g creatinine). No significant difference was found when e-cigarette (1163.02 ng/g creatinine) and IQOS smokers were compared (1088.3 ng/g creatinine). Conclusion: People who use e-cigarettes and IQOS may be at higher risk of genotoxicity than those who do not use and are not exposed to any tobacco products. Furthermore, the usage of flavoring additives in e-cigarettes contributed to additional genotoxic damage risks.