Prevention of Cigarette Smoke-Induced Lung Cancer by Dietary Selenium

描述（由申请人提供）： 肺癌是美国癌症死亡的主要原因。肺癌的主要危险因素是吸烟。预防肺癌发展的一种策略是增加具有化学预防潜力的营养素的消耗。在流行病学和实验研究中发现，膳食硒可以抑制几种癌症的发展。1996年的一项干预研究发现，服用硒补充剂的人患几种癌症的发病率较低，包括肺癌。然而，还没有建立动物模型表明膳食硒抑制香烟烟雾诱导的肺癌。在这些研究中，我们建议在A/J小鼠模型中检验膳食硒抑制香烟烟雾诱导的肺癌的假设。小鼠将被喂食含有推荐水平的硒以及两个更高水平的硒的饮食，以确定补充硒是否会抑制肺肿瘤发生。在其他研究中，小鼠将暴露于香烟烟雾较短的时间，以确定膳食硒是否抑制香烟烟雾诱导细胞色素P-450活性，氧化DNA损伤和细胞增殖。这些研究将确定A/J小鼠模型是否适用于研究膳食硒的影响。如果成功，该模型可以进一步研究，以确定硒抑制的分子机制，从而为预防肺癌的可能饮食建议提供机制基础。

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.