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Cytotoxicity and Stress Induction by Thirdhand Smoke

Institution: University of California, Riverside
Investigator(s): Prudence Talbot, Ph.D.
Award Cycle: 2015 (Cycle 24) Grant #: 24RT-0037H Award: $443,453
Subject Area: Environmental Exposure/Toxicology
Award Type: Research Project Awards
Abstracts

Initial Award Abstract

 Thirdhand smoke (THS), tobacco smoke that settles on indoor surfaces, such as drapes, upholstery and carpets, contains secondhand smoke chemicals which are known to kill cells and induce cancer. Nicotine in THS can be converted to cancer-causing agents during aging. While little is known about how THS affects human health, data have shown that it produces changes in cells that could lead to cancer and other adverse health effects. This research on THS and human health identifies and investigates effects of the most toxic constituents of THS on cell stress and death in animal and human cells. The goal is to generate scientific information to inform the public and officials to create rational policies for the regulation of indoor smoking and remediation of areas contaminated by THS. 

Data from our previous experiments show that THS is characterized by: (1) volatile organic chemicals that disperse over time and (2) residual chemicals that persist for many months. Both types of chemicals were cytotoxic, killing cells at higher doses and inducing stress at non-lethal doses. The goal of the proposed research is to study cell toxicity of chemicals extracted from fabric samples exposed to smoke in the laboratory and in fabrics from filed sites including homes and casinos; measure the amounts of chemicals deposited during various lengths of time; identity the volatile chemicals that induce cytotoxicity; and study molecular indicators that THS-exposed cells are stressed and/or dying. This research will compare results from cultured human cells growing in vitro, literally “in glass,” and cell and blood samples from THS-exposed mice and humans.

The first Specific Aim will measure THS toxicity in human cells and then identify the specific molecules that are targeted by THS. Fabric samples exposed to THS in a laboratory environmental chamber and collected from homes and casinos will be carpet, upholstery and drapes, which are likely to act as long-term repositories of THS chemicals. This Aim will use new assays to measure cellular processes affected by THS. One assay will examine videos of living cells to observe cell stress, and use software to detect subtle changes not apparent to human observers.

The second Specific Aim will identify the volatile chemicals in THS-exposed fabrics that cause cytotoxicity and stress and identify which cell functions are targets of the most potent chemicals.

The third Specific Aim will measure biological markers in cells that display an adverse reaction to THS in human fluid/cell samples and animal tissues, and compare these results with cell data from Aims #1 and 2. Biomarkers of harm include changes in the expression of genes that result from cell stress and reactions to toxicity.

The project will: (1) provide new quantitative data on cell stress and death caused by THS chemicals extracted from fabrics exposed in the laboratory and in casinos and homes; (2) determine which types of fabrics retain the highest concentrations of THS chemicals and are most harmful to cells, (3) compare THS sensitivity in cells from embryos and adults, (4) identify the cellular processes and molecular targets affected by THS; (5) identify specific volatile chemicals in THS that cause cell death/stress, (6) compare how the concentrations of nicotine and other THS chemicals in cultured cells compare to actual concentrations in humans and mice exposed to THS, and (7) determine if biomarkers of harm are elevated similarly in cultured cells, mice and humans exposed to THS. This is the first study to compare the toxicity of THS across cell, animal, and human models. Data will immediately inform regulatory agencies of the types of potential harm from various fabrics, exposure times, dosages, cell types, cell targets, and stages of development. The experiments also will accelerate future studies of THS by validating cell, mouse, and human cell study models and documenting measurements of THS harmful effects in these different cells