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Tobacco-altered tissue of the mouth may promote oral cancer

Institution: Lawrence Berkeley National Laboratory
Investigator(s): Ana Krtolica, Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11IT-0138 Award: $113,120
Subject Area: Cancer
Award Type: Inno Dev & Exp Awards (IDEAS)

Initial Award Abstract
Cancers of the mouth and lip are the most common types of cancer in smokeless tobacco, pipe and cigar users. Cigarette smokers also have a higher chance of developing oral cavity cancers relative to non-smokers. While it is well documented that both cigarette smoke extract and smokeless tobacco extract contain multiple compounds that may induce mutations leading to cancer, little is known about the exact mechanisms involved in tumor development in chronic tobacco users.

We propose to test the hypothesis that nicotine and other tobacco constituents released into the mouth during smokeless tobacco use and/or smoking may induce changes in the tissue structure of the mouth that promote cancer growth and development. In this paradigm, tobacco's ability to cause cancers through induction of mutations may be enhanced by its effect on cells in the supporting tissue.

We already know that tobacco constituents can cause tumors through their ability to produce genetic mutations. Our goal is to look for a primary or contributory role of mechanisms that involve other cell types that lie adjacent to tumors. A good analogy for our work is the role of the soil in the development of seeds. Tobacco constituents alter genetic make-up of seeds by causing mutations. Here, we test the hypothesis that the soil is also affected, which in turn promotes development of the plant from the seed i.e., formation of tumors. These experiments are important because under normal conditions, the supporting tissue regulates the growth and behavior of the cells above it. If this control is relaxed, precancerous cells have greater probability of developing into cancer. Thus, we plan to apply established cell culture model systems for studying the influence of supporting cells on tumor development and evaluate the role of altered supporting cells in tobacco-related cancer.

This study seeks to fill a gap in our knowledge of cellular events involved in tobacco-related cancer progression. It will determine the influence of the tobacco-altered tissue environment and its contribution to tumor development, and provide potential new strategies for clinical intervention. If our hypothesis is correct, this project will lay the ground for a more detailed exploration into new ways to curb the negative effects of tobacco in promoting cancer, and open new strategies for cancer prevention immediately after tobacco use cessation. In doing so, we hope to uncover new targets for drug intervention.