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Double-strand Break by THS: Implications for Tobacco Cancer

Institution: Lawrence Berkeley National Laboratory
Investigator(s): Altaf Sarker, Ph.D
Award Cycle: 2017 (Cycle 26) Grant #: 26IR-0017 Award: $581,626
Subject Area: Environmental Exposure/Toxicology
Award Type: High Impact Research Project Award

Initial Award Abstract

Smoking is the major risk factor for the development of lung cancer. According to the American Lung Association, an estimated 158,000 people are expected to die from lung cancer this year. In the US, that number represents 27% of all cancer deaths. The adverse biological and health effects of active smoking and second-hand smoke have been analyzed in cells and in animal models. Most recently, potential health concerns have been raised about thirdhand smoke (THS), a much less understood type of smoke exposure defined as residual tobacco smoke adsorbed onto indoor surfaces after active smoking has ceased. Although it is considered as a potential health hazard, the relationship of THS to cancer initiation remains largely unknown. We have previously reported the induction of DNA strand breaks in cultured human cells following exposure to THS, suggesting that THS causes DNA damage. However, the nature of the DNA strand breaks is not understood, nor is the mechanism of generating the damage or how it may be repaired. This information is critical for risk assessment of disease development related to THS exposure, especially for carcinogenesis. A large consortium of scientists from different disciplines is now working on THS-related health hazard analysis, and they have identified the chemical constituents of THS. This work has made significant contributions to our understanding of the relationship between these chemicals and their potential to damage DNA. We have now generated preliminary information showing the induction of DNA double-strand breaks (DSBs) following exposure of lung cells to THS in standard 2D culture. These results are important since DSBs are the major source of instability in the human genome, which is a key step in carcinogenesis. In this proposal, we will investigate THS-induced DNA damage in a 3D cell culture system that more closely resembles human tissue exposure. We have assembled a highly competent team to accomplish the proposed studies, and the information from this project will be key to understanding the mechanism of THS exposure-related cancer development. Ultimately, we anticipate that the results will provide information helpful to implementation of legislative action and behavioral changes that will lead to decreased smoking in the indoor environment.