E-Cigarette Smoke Poses Threat to DNA Repair Activity

E-cigarette smokers have a high risk of developing lung and bladder cancer, as well as certain heart diseases due to carcinogenic e-cigarette smoke (ECS), according to a study published in the Proceedings of the National Academy of Sciences.

E-cigarettes were developed as a tool for tobacco smokers to receive nicotine without the harmful effects of burning tobacco. This would be a way to reduce their smoking habits and their addiction to nicotine. However, 18 million people have started to smoke e-cigarettes as they are considered a healthy way to quit smoking.

The researchers measured the carcinogenicity of ECS and compared it to tobacco smoke (TS) to observe if there is DNA damage created by ECS. Mouse models were used to measure DNA damage and repair while the effect of ECS on the susceptibility to mutations on cultured human cells.

Twenty mice were split into 2 groups and exposed to ECS (10 mg/mL, 3 hours/day, 5 days/week) for 12 weeks. This dosage amount and length of time is equivalent in human terms to light e-cigarette smoking for 10 years. Two major DNA-repair mechanisms in mouse lung tissues were examined: nucleotide excision repair (NER) and base excision repair (BER). It was found that in the lung tissues of ECS-exposed mice had significantly lower levels of NER and BER than filtered air-exposed mice.

Nicotine is unable to bind to DNA, yet the inhaled nicotine-derived nitrosamine ketone (NNK) is metabolized into methyldiazohydroxide (MDOH) which can methylate deoxyguanosines and thymidines in DNA. In humans, it was shown that metabolites of nicotine and NNK mutate DNA-repair proteins and affect DNA-repair activity and repair protein levels in human lung and bladder epithelial cells.

While nicotine is not carcinogenic, large amounts of the stimulant turn into tobacco-specific nitrosamines (TSA), like NNK, through nitrosation. TSA have proved to be carcinogenic in animal models. Nitrosation occurs in the human body when ECS is inhaled, putting e-cigarette smokers at risk for inhaling carcinogens.

“We also found that nicotine and NNK can enhance mutational susceptibility and induced tumorigenic transformation of human lung and bladder epithelial cells,” the authors concluded. “Based on these results, we propose that ECS is carcinogenic and that [e-cigarette] smokers have a higher risk than nonsmokers to develop lung and bladder cancer and heart diseases.”

References

Lee HW, Park SH, Weng MW, et al. E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. Proc Natl Acad Sci. 2018. Published online ahead of print January 29, 2018.