Role of intracellular signals in tobacco-related disease
Abstracts
Initial Award Abstract |
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Tobacco smoke contains a cancer causing agent, arsenic. A person is exposed to the toxic arsenic when smoking or inhaling secondhand smoke. One would have a much higher chance of getting lung cancer or other tobacco-related diseases than someone not exposed to arsenic.
To understand how arsenic damages cells, I will isolate and study one of the critical cellular proteins that stop to function after exposure to arsenic. This protein, called an arsenic sensitive phosphatase, is important in intracellular communication. When it loses its normal function, cells are not able to control their intracellular traffic effectively. Accidents occur and damages build up over time. Once sufficient damage is done, the cells would become cancerous. Therefore, this protein can suppress cancer development when it works normally and may be called a tumor suppressor. This study is designed to gain knowledge about this protein that is affected by arsenic. The knowledge would be important in designing new drugs that could restore its function. More importantly, the knowledge would allow us to modify our life style to prevent cancer. For example, a diet containing a lot of green vegetables, such as broccoli, may offer protection against carcinogens such as arsenic. Therefore, this study is directly relevant to the goal of reducing the human and economic cost of tobacco-related disease. |
Final Report |
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Tobacco smoke contains a cancer causing agent, arsenic. A person is exposed to the toxic arsenic when smoking or inhaling secondhand smoke. One would have a much higher chance of getting lung cancer or other tobacco-related diseases than someone not exposed to arsenic.
In a step towards understanding how arsenic damages cells, I have identified a critical cellular protein that stops to function after exposure to arsenic. This protein, called MKP-1 (mitogen activated protein kinase phosphatase 1), is important in intracellular communication. When it loses its normal function, cells are not able to control their intracellular signals effectively. Accidents occur and damages build up over time. Once sufficient damage is done, the cells become cancerous. Therefore, this protein can suppress cancer development when it works normally and may be called a tumor suppressor. Arsenic also perturbs intracellular signals in a number of ways that remain to be examined.
The identification of specific intracellular targets of arsenic would be important in designing new drugs that could prevent its carcinogenic activity. More importantly, the knowledge would allow us to modify our life style to protect our cells from oxidative damage. For example, a diet rich in antioxidants, found in many green vegetables, may offer protection against carcinogens such as arsenic. This study provides further evidence about the involvement of tobacco in human diseases and suggests methods to treat and prevent such diseases. |
