Carcinogenesis cellular model for identifying preventive agents

University Of Tennessee Knoxville, Knoxville TN

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Abstract

Summary The ultimate goal of this project is to further develop an efficient cellular model and methods to identify dietary agents for preventing human cancers induced by tobacco and environmental carcinogens. Studies have suggested that exposures to tobacco and environmental carcinogens increase the risk of cancer development in humans. Growing evidence suggests vegetables and fruits can play a protective role in human healthcare by preventing cancers and other diseases. However, there is a serious gap in our understanding of how dietary constituents prevent human cancers associated with chemical carcinogens. The rationale for this project is to establish a low-cost cellular model and methods to study cellular and molecular mechanisms for dietary agents in the prevention of cellular carcinogenesis induced by tobacco and environmental carcinogens. Using cell technology, we have been developing a carcinogenesis-cellular model mimicking chronic exposures of human breast epithelial cells to low doses (levels detected in smokers) of carcinogens. We have been able to induce cells to progressively acquire cancerous properties, from an immortalized non-cancerous stage through identifiable precancerous sub-stages to a cancerous stage. With gene chip technology, our cellular model serves as a system to reveal the molecular markers of carcinogens in the progressive transformation of human epithelial cells. The central hypothesis is that the identifiable, acquired cancerous properties and molecular markers of cellular carcinogenesis are able to serve as biological and molecular endpoints for the prevention of breast cell carcinogenesis, which will then allow us to determine biological and molecular activities of preventive agents for protecting human cells from carcinogenesis. To test this hypothesis, we will address the capability of our carcinogenesis-cellular model to reveal the ability, the mode of action, and the molecular markers associated with dietary suppression of cell acquisition of cancerous properties induced by individual carcinogens. Success of this study will empirically validate our approach of identifying preventive agents to block carcinogenesis associated with tobacco and environmental pollution, and create a foundation for studying the molecular mechanisms involved in the dietary prevention of carcinogen-related cancers. The broad impact is expected to benefit the whole of society by providing an efficient cellular model to identify dietary constituents for formulating diets or supplements that can prevent human cancers related to tobacco exposure and environmental pollution. Narrative Success of this study will empirically validate our approach of identifying preventive agents to block carcinogenesis associated with tobacco and environmental pollution, and create a foundation for studying the molecular mechanisms involved in the dietary prevention of carcinogen-related cancers. The broad impact is expected to benefit the whole of society by providing an efficient cellular model to identify dietary constituents for formulating diets or supplements that can prevent human cancers related to tobacco exposure and environmental pollution.