E-Cigarette Smoke Linked to Lung Cancer
by Dr. C.H. Weaver M.D. 10/2019
Currently 3.6 million Junior and high school students use e-cigarettes as a result of messaging that suggests they are void of significant health risks. Recently however new concerns have been raised about the risk of e-cigarettes based on reports of direct lung toxicity.
Investigators from NYU have now reported that exposure to e-cigarette smoke caused mice to develop lung cancer according to a new study published in the prestigious Proceedings of National Academy of Sciences. The study found that 22% of mice exposed to e-cigarette smoke with nicotine for 54 weeks developed lung adenocarcinomas. None of the 20 mice from the study exposed to the same e-cigarette smoke without nicotine developed cancer. (1)
The study also found that 57% of mice exposed to e-cigarette smoke developed pre-cancerous changes in cells that line the bladder.
According to the study author, Dr. Tang “Tobacco smoke is among the most dangerous environmental agents to which humans are routinely exposed, but the potential of e-cigarette smoke as a threat to human health is not yet fully understood.” Our study results in mice were not meant to be compared to human disease, but instead argue that e-cigarette smoke must be more thoroughly studied before it is deemed safe or marketed that way.”
Nicotine and Nitrosamines
The question of whether nicotine itself, separate from tobacco smoke, causes cancer is controversial because of conflicting study results over time that used oft-criticized methods. Almost all researchers agree, however, that chemicals added during the curing of tobacco—nitrate and nitrite—can cause a reaction called nitrosation, or the addition of a particle called a nitrosonium ion, the authors say.
This is known to convert nicotine into nitrosamines such as N-nitrosonoricotine (NNN) and nicotine-derived nitrosamine ketone (NNK), which are proven carcinogens in mice and humans.
Conventional thinking, says Dr. Tang, has been that smoke from cured tobacco deposits nitrosamines into a smoker’s organs and blood. Nitrosamine blood tests are the best measure of their potential to cause cancer. Such tests in a previous study found that levels of a compound related to NNK, called NNAL, were 95 percent lower in e-cigarette smokers than in tobacco smokers, leading some experts to conclude that a switch to e-cigarettes might save millions of lives. (3)
Dr. Tang’s team had shown previously that e-cigarette smoke induces DNA damage in the mouse lung and bladder, and that nitrosation in cultured human lung and bladder cells converts nicotine into derivatives that increase DNA code changes, or mutations, with the potential to transform normal cells into cancer cells. Specifically, the earlier study found that nicotine is transformed into nitrosamines, then into DNA damaging agents, which ultimately form DNA adducts. (4)
The current study results confirm that nicotine from e-cigarette smoke can cause cancer in the lungs, and precancerous growth in the bladders, of mice. Furthermore, the results argue that nicotine, once inside cells, is converted into nitrosamines that do not leave cells and, therefore, could never be captured by tests that measure nitrosamine levels outside of cells, for example blood tests, says Dr. Tang.
Further research will focus on expanding the number of mice studied, to shorten and prolong e-cigarette exposure times, and to further investigate the genetic changes caused by e-cigarette smoke.
Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice
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.
E-Cigarettes: Use, Effects on Smoking, Risks, and Policy Implications
Since e-cigarettes appeared in the mid-2000s, some practitioners, researchers, and policy makers have embraced them as a safer alternative to conventional cigarettes and an effective way to stop sm...
Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study
Lion Shahab, PhD; Maciej L. Goniewicz, PhD; Benjamin C. Blount, PhD; Jamie Brown, PhD; Ann McNeill, PhD; K. Udeni Alwis, PhD; June Feng, PhD; Lanqing Wang, PhD; Robert West, PhD
E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells
E-cigarette smoke (ECS) delivers nicotine through aerosols without burning tobacco. ECS is promoted as noncarcinogenic. We found that ECS induces DNA damage in mouse lung, bladder, and heart and reduces DNA-repair functions and proteins in lung. Nicotine and its nitrosation product 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone can cause the same effects as ECS and enhance mutations and tumorigenic cell transformation in cultured human lung and bladder cells. These results indicate that nicotine nitrosation occurs in the lung, bladder, and heart, and that its products are further metabolized into DNA damaging agents. We propose that ECS, through damaging DNA and inhibiting DNA repair, might contribute to human lung and bladder cancer as well as to heart disease, although further studies are required to substantiate this proposal.