E-cigarettes deliver nicotine to users by aerosolizing “e-liquid” that is a solution containing nicotine and flavoring agents. The solvent used to dissolve these elements usually consists of propylene glycol and glycerin (PG/VG), which is recognized by the FDA as “generally recognized as safe” (GRAS) for ingestion (eating), so people generally don’t worry about it. In 2019 the FDA proposed updating its list of Harmful and Potentially Harmful Compounds (HPHC) in tobacco products to add several things, including PG/VG, but never issued a final updates list. considered to have , nicotine and flavoring agents.
A new paper by Marcel Arias Badia, Larry Fong and I, together with other UCSF colleagues just published, E-cigarette exposure disrupts antitumor immunity and promotes metastasis, provides strong experimental evidence (in mice) that PG/VG promotes tumor growth and occurrence of metastasis across several cancer types (melanoma, colorectal, and prostate cancers). PG/VG stimulates these processes in a dose-dependent manner and nicotine often, but not always, amplifies these effects.
These findings are important because most discussion of e-cigarettes and cancer has ended with the fact that nicotine is not a carcinogen (i.e., induces tumors). (PG and VG are not carcinogens either.) This focus on carcinogenesis ignores the possibility that toxicants can accelerate tumor development even if they don’t induce the initial tumor.
Our paper reports an extensive set of experiments in which we (1) exposed isolated cancer cells to PG/VG and/or nicotine, (2) exposed tumor cells before injecting them into mice, and (3) had mice breathe e-cigarette aerosol before injecting tumor cells all made the cancers develop faster and metastasize more.
We also showed that these effects were mediated by specific changes to the ability of the immune system to fight cancers in addition to promoting tumor-intrinsic mechanisms leading to changes in tumor cell survival and invasion.
We conclude
In 2012, the Food and Drug Administration established a list of Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke (HPHC), which is dominated by toxicants in cigarette smoke. The HPHC list provides key metrics for assessing the harmfulness of tobacco products. In 2019 the FDA proposed adding 19 compounds to the HPHC list, including propylene glycol and glycerol, to reflect compounds in ecigarettes. While e-cigarette components may induce lower carcinogenesis (although there is little data beyond lower biomarkers of exposure), there are many indirect effects that must be considered when assessing their health impact, including promotion of metastasis or immunosuppressive infiltration documented here. The results presented in this study underscore the consideration of propylene glycol as a harmful component given its widespread use in e-cigarettes as well as heated tobacco products.
Our results demonstrate new potential risks associated with ecigarettes. Future assessments of the safely of e-cigarettes should include not only incidence of cancer, but also acceleration of cancers caused by other agents. [citations deleted]
Here is the abstract:
Electronic cigarettes (e-cigarettes) are thought to pose low risk of cancer because the components of e-cigarette liquid are not carcinogens. We analyzed the effects of the two major components, PG/VG and nicotine, on tumor development in preclinical models. We found that PG/VG promoted tumor cell migration in migration assays and contributed to more aggressive, metastatic, and immunosuppressive tumors in vivo, aggravated by the presence of nicotine. Whole body exposure of mice to PG/VG and nicotine rendered animals more susceptible to developing tumors with high frequencies of infiltrating proinflammatory macrophages expressing IL-6 and TNFα. Moreover, tumor-infiltrating and circulating T cells in e-cigarette exposed mice showed increased levels of immune checkpoints including CTLA4 and PD-1. Treatment with anti-CTLA4 antibody was able to abrogate metastasis with no detrimental effects on its ability to induce tumor regression in exposed mice. These findings suggest that the major components used in e-cigarette fluid can impact tumor development through induced immunosuppression.
The full citation is: Arias-Badia M, Pai C-CS, Chen P, Chang A, Lwin YM, Srinath A, Gotts JE, Glantz SA, Fong L (2024) E-cigarette exposure disrupts antitumor immunity and promotes metastasis. Front. Immunol. 15:1444020. doi: 10.3389/fimmu.2024.1444020. It is available for free here.
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