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Electronic cigarettes are rapidly moving into consumer markets, and sales in the United States are expected to exceed 1 billion dollars this year. Because electronic cigarettes deliver nicotine without burning tobacco, they may offer an alternative for smokers who cannot break their nicotine addiction. However, little is known about electronic cigarette emissions or the health problems they produce, making it difficult for regulatory agencies to establish polices for their manufacture, sales, and marketing. Our long-term objective is to understand how electronic cigarettes affect human health and to contribute to the scientific foundation that will be used to establish rational policies for regulating electronic cigarettes. Our Preliminary Data demonstrate the presence of metals, including metal nanoparticles, in the aerosol of a leading brand of electronic cigarette. Two of the metals in this aerosol are carcinogens, while others are potential toxicants. The presence of metal nanoparticles in electronic cigarette aerosol is of particular concern as nanoparticles are often more toxic than larger sized particles of the same metals. The goal of the proposed research is to identify and quantify the metal content of electronic cigarette aerosols from a broad spectrum of products and designs, to examine the toxicity of aerosol metals on cells and DNA, and to examine biomarkers of metal exposure and effect in human electronic cigarette users.
In our first Specific Aim, we will identify and quantify metals in electronic cigarettes from various brands and styles and determine how metal concentrations correlate with electronic cigarette design. Aerosol will be sampled from new products over two years to determine how metal emissions vary as these products evolve. Metals will be analyzed using an advanced analytical technique that will both identify and quantify metals in electronic cigarette aerosols. Characterization of particle structure and size will be done using scanning and transmission electron microscopy coupled with a method that will identify metals in samples that are examined in the electronic microscope. In the second Specific Aim, we will determine if aerosols with metals produce adverse effects in human cells using assays that measure cell health and DNA damage, in combination with a novel liver cell metabolizing assay. Human embryonic stem cells, which will be used to model an early stage of prenatal development, are generally more sensitive to toxicants than adult cells and will be compared with human pulmonary fibroblasts, which model a differentiated adult cell. To confirm that toxic effects are due to metals, some experiments will be done with aerosols from which metal has been removed. We will also test the hypothesis that aerosols which are toxic induce reactive oxygen species which cause oxidation of cellular proteins and DNA.
In Aims 1 and 2, metals in electronic cigarettes will be compared to metals found in three popular brands of combustible cigarettes. In Specific Aim #3, we will use metal biomarkers to quantify metal exposure and effect in humans who use electronic cigarettes, determine which metals are taken up by cells in humans, if metal uptake by cells includes nanoparticles, and determine whether metals migrate to the bloodstream and are excreted in the urine. Biomarkers of metal effect will establish if electronic cigarettes produce adverse affects in users that may foreshadow disease, including cancer. Our project will generate new data on: (1) the metal content of electronic cigarette aerosols across a broad spectrum of evolving products, (2) the toxicity of the metals in electronic cigarette aerosols and their mechanism of action, (3) the relative sensitivity of embryonic vs. differentiated adult cells to electronic cigarette aerosol metals, and (4) the absorption, excretion, and the biological effects of metals on human electronic cigarette users. These data, the first of their kind, will contribute to a foundation of science upon which the FDA, as well as local and state agencies, can develop regulatory policies to protect consumers’ health and minimize future public health problems. |
