Evaluating the Toxicity of Tobacco Products Using In Vitro 3D Tissue Models
Principal Investigator: Robert H. Heflich/Patricia Richter
Funding Mechanism: JV
ID number: E0746801
Award Date: 11/3/2011
Institution: National Center for Toxicological Research
Tests for comparing the relative toxicity of tobacco products are not presently available due to the lack of appropriate in vitro and validated assays. Researchers have developed and validated human in vitro 3D tissue models for toxicity testing; 3D airway models have an air-tissue interface similar to that of the human respiratory tract, a target of tobacco smoke exposure. This study will investigate preliminary 3D tissue model data indicating that tobacco smoke exposure results in cytotoxicity, induction of cytochrome P450 drug metabolizing enzymes (CYPs), and inflammatory responses in the human airway. In addition, investigators will evaluate endpoints suitable for use in tissue models (including histopathological evaluations), endpoints related to intercellular interactions, and biomarkers developed by NCTR Project ID E0744701. Study aims are: (1) to identify 3D tissue models that may be applicable for evaluating tobacco product toxicity; (2) to perform preliminary studies to develop and verify 3D tissue model baseline characteristics and measurement methods and to identify positive controls for major toxicity endpoints; and (3) to evaluate the ability of these models to differentiate between toxicity and inflammation produced by a series of cigarette smoke condensates. This study will provide information that may inform the generation of toxicity data using models that are human-based, untransformed and simulate normal human tissue targets for tobacco, thus mitigating the need for animal studies.