Prevention of Cigarette Smoke-Induced Lung Cancer by Dietary Selenium

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DESCRIPTION (provided by applicant): Lung cancer is the leading cause of death from cancer in the United States. The major risk factor for lung cancer development is cigarette smoking. One strategy for preventing lung cancer development is to increase the consumption of nutrients which have chemopreventive potential. Dietary selenium has been found to inhibit the development of several types of cancer in epidemiological and experimental studies. A 1996 intervention study found that individuals who consumed selenium supplements developed a lower incidence of several types of cancer, including lung cancer. However, no animal model has ever been established showing that dietary selenium inhibits cigarette smoke-induced lung cancer. In these studies, we propose to test the hypothesis that dietary selenium inhibits lung cancer induced by cigarette smoke in the A/J mouse model. Mice will be fed diets containing the recommended level of selenium as well as two higher levels to determine if supplemental selenium will inhibit lung tumorigenesis. In other studies, mice will be exposed to cigarette smoke for shorter periods of time to determine if dietary selenium inhibits the induction of cytochrome P-450 activity, oxidative DNA damage, and cell proliferation by cigarette smoke. These studies will determine if the A/J mouse model is valid for studying the effects of dietary selenium. If successful, the model can then be further studied to determine the molecular mechanisms by which selenium is inhibitory, and thus provide a mechanistic basis for possible dietary recommendations for the prevention of lung cancer.