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Evaluation of tobacco and e-cigarette genotoxicity

Institution: Beckman Research Institute of the City of Hope
Investigator(s): Timothy O'Connor, Ph.D.
Award Cycle: 2016 (Cycle 25) Grant #: 25IP-0020 Award: $408,000
Subject Area: Environmental Exposure/Toxicology
Award Type: High Impact Pilot Award

Initial Award Abstract

In response to overwhelming evidence that tobacco smoke is a carcinogen and subsequent dropping sales, tobacco companies have developed products that they market as being less dangerous. One product in particular, e-cigarettes has seen tremendous growth in usage within the last 4 years that has eclipsed the use of most other tobacco alternative products. The use of e-cigarettes removes much of the stigma associated with the use of conventional cigarettes and some countries have seen e-cigarettes marketed as helpful in smoking cessation efforts. However, other published work has suggested that e-cigarettes still pose health hazards that lead people to eventually using cigarettes. Additionally, e-cigarettes are often sold with flavoring ingredients such “cherry” or “vanilla bean” that can make e-cigarettes more attractive to a wider non-smoking audience, including young people, which could lead them to use cigarettes. Thus, a much broader group could be exposed to these e-cigarettes than smokers who are interested in reducing their health risk from tobacco smoke. Moreover, other evidence indicates that e-cigarette use does not decrease long-term tobacco use. Despite these potential risks, there is still only limited research data available on long-term health risks (for example, increased risk of developing cancer) of e-cigarettes. Until now, researchers focusing on e-cigarettes have mainly evaluated the acute toxicity of e-cigarettes; in other words how many cells die and how many survive after exposure to e-cigarettes or their vapors. However, cancers generally develop in normal cells that survive exposure to chemicals or radiation, but have changes in their DNA that make them become cancerous. One way to predict the potential carcinogenicity of a chemical, such as e-cigarette liquid, is by evaluating its genotoxicity, which indicates the DNA changes induced by chemicals or radiation. Evaluating genotoxicity is a better predictor of cancer risk than approaches that focus on measuring cell survival after exposure to a chemical. Genotoxicity can be subdivided into changes in a single DNA base (known as a point mutation) and large changes in chromosomes (known as gross chromosomal rearrangements in which large pieces of DNA are lost or moved to incorrect locations). Both types of genotoxicity increase the chances that cells will become cancerous, and therefore, both types of changes must be evaluated. Our goal in this proposal is to develop methods to evaluate both types of genotoxicity for e-cigarettes, and thus the cancer risks that e-cigarettes present to humans. We will develop and use innovative methods that allow the genotoxicity of e-cigarettes and their vapors to be evaluated in human cells, as compared to mouse or rat cells, which are currently more often used for these types of studies. This means our results will be more directly applicable to human health. We will also determine which of the major DNA repair mechanisms contribute to survival of cells exposed to e-cigarettes. Currently, hundreds of e-cigarette liquids are available in California, and this selection is too vast for all e-cigarettes to be studied during the time frame of this proposal. Therefore we will examine representative e-cigarettes and their vapors that are, at this time, considered to be among the 3 most used brands. To the best of our knowledge, this study will provide the first information about the genotoxicity of e-cigarettes in human cells. We expect the resulting data will reliably estimate the cancer risk posed to humans by e-cigarettes and yield information that can indicate DNA repair pathways to investigate that would assist in identifying early indicators of cancer, and potentially improve early diagnosis of this disease. Collectively, the data obtained and methods developed in this project will improve our ability to assess the potential human health impact of e-cigarettes and we will work with our community groups to publicize our results. Such data will enable policymakers to identify products that could increase cancer risk for users and to make informed decisions regarding regulatory policy to protect the public’s health.