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Use of New Technologies to Develop Biomarkers of Harm for New Tobacco Products

Principal Investigator: William Salminen/Maocheng (Tony) Yang

Funding Mechanism: JV

ID number: E0744711

Award Date: 6/22/2012

Institution: National Center for Toxicological Research

Omics technologies (i.e., genomics, metabolomics, and proteomics) have the potential to identify new biomarkers of harm from various types of products (e.g., drugs and general chemicals) and provide more sensitive indicators of cellular injury.  Gene expression changes in target tissue or cells often occur before clear phenotypic signs of injury are observed.  In this study, investigators will conduct omics analyses to detect subtle changes in cellular function in response to toxicants in tobacco smoke and smokeless tobacco products, and will identify biomarkers that may inform the evaluation of new tobacco products making reduced health risk claims. Study aims are: (1) to conduct in vitro and in vivo toxicological assessments to identify biomarkers, quantify toxicities, and establish dose responses for chemicals of interest to the Center for Tobacco Products (CTP); (2) to improve the predictive value of toxicological assays by determining biological mechanisms of action and applying translational studies using traditional, pharmacogenomic, proteomic, metabolomic, and bioimaging approaches; and (3) to develop, evaluate and compare in vitro and in vivo toxicity testing models and computer-assisted toxicology knowledge bases in order to provide quantitative data for improved safety assessments. This study may provide a foundation for discovering new biomarkers of harm in key cell types (i.e., lung and heart cells) affected by tobacco smoke; these biomarkers could potentially then be used in the clinical setting to support tobacco use risk assessment.

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