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Proteomic Assessment of Heavy Metal Mixture Exposure

Institution: University of California, Riverside
Investigator(s): John Prins, Ph.D.
Award Cycle: 2012 (Cycle 21) Grant #: 21FT-0086 Award: $45,000
Subject Area: Environmental Exposure/Toxicology
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract

Tobacco use is the leading cause of preventable death and is estimated to kill more than 5 million people worldwide each year. Tobacco-related diseases including cancer, lung disease, heart disease and stroke, results as a biological consequence of repeated exposure to the toxic constituents found in tobacco and its smoke. More than 4,000 chemicals have been identified in tobacco smoke, at least 250 of which are known to be harmful and more than 50 of which are known to cause cancer. Non-smokers can come in contact with these toxic compounds through second and thirdhand smoke exposure. Secondhand smoke refers to the passive inhalation of smoke, whereas thirdhand smoke (THS) is a relatively new term used to describe the residual contamination from tobacco smoke that remains on surfaces and the smokers themselves. There is a growing body of evidence that this lingering tobacco residue represents a significant health risk.

THS consists of complex mixtures of toxic particulates such as nicotine, tobacco specific N’-nitrosamines (TSNAs), and heavy metals, which can cling to walls, ceilings, carpets, clothing, and hair, allowing for continual exposure to these toxins well beyond periods of active smoking. People can become exposed to these toxic residues through dermal contact with contaminated areas or by inhalation of toxic particulate matter. The health risk associated with THS most likely are not tied to a single toxic constituent but are a result of cumulative simultaneous exposure to multiple toxicants. In order to improve risk assessment and gain a true understanding of how THS exposure can affect biological systems, it is necessary to investigate the interactive effects of multiple toxicants.

Heavy metals and TSNAs represent two important classes of carcinogens found in THS residues. The heavy metal cadmium (Cd) is a known carcinogen that has been detected in significant amounts in tobacco and its smoke. Cd exposure can lead to the formation of a variety of malignancies, including leukemia and cancers of the lung and prostate. Other well-known toxic constituents of tobacco are the TSNA’s, which are considered to be some of the most carcinogenic compounds found in tobacco and THS. Although a large body of literature exists on the individual effects of Cd on various cellular processes in a variety of biological systems, little is known about the synergistic effects of Cd in combination with other tobacco-related toxins. Investigations into the interactive effects of Cd in combination with other toxic tobacco compounds such as TSNAs would give a more accurate perspective on the molecular mechanisms targeted by toxic THS constituents.

Although the potential toxicological importance of chemical mixtures research is well recognized, few studies have been conducted with mixtures of tobacco related heavy metals and other, toxic tobacco constituents. We propose to investigate the affects of Cd and TSNA mixtures on human cells by determining changes in protein levels induced by exposure to heavy metals and TSNAs using proteomics. Proteomics can generally be defined as a technique used for the large-scale study of proteins, particularly their structures and functions. Proteomics is ideal for these types of studies since it allows for the analysis of a large number of proteins simultaneously from a single experiment. Since proteins are essential constituents of living cells and are necessary for the proper functioning of an organism, measuring changes in protein levels at a given time can provide valuable information on how toxic substances are affecting biological systems. The results from these studies will help further our understanding of how tobacco use can affect biological systems by providing valuable insight into the interactive effects associated with tobacco related heavy metals and TSNAs on biological systems. The data from this study may be important for improved risk assessment by elucidating the biochemical mechanisms that contribute to the adverse health effects of THS exposure.