Prevention of Cigarette Smoke-Induced Lung Cancer by Dietary Selenium

通过膳食硒预防香烟烟雾诱发的肺癌

• 批准号: 7475778
• 负责人: HOWARD P GLAUERT
• 金额: $ 7.33万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7475778
• 关键词: 8-hydroxy-2' -deoxyguanosine; A/J Mouse; Animal Model; Antioxidants; Bromodeoxyuridine; Cause of Death; Cell Proliferation; Cells; Chemopreventive Agent; Consumption; Cytochrome P-450 CYP1A1; Cytochrome P450; Development; Diet; Dietary Selenium; Human; Incidence; Individual; Intervention Studies; Label; Lung; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Modeling; Molecular; Mus; Nutrient; Oxidative Stress; Prevention; Principal Investigator; Proteins; Rate; Recommendation; Risk Factors; Selenium; Smoke; Testing; Time; United States; Week; base; cancer type; cigarette smoke-induced; cigarette smoking; cigarette smoking; enzyme activity; feeding; glutathione peroxidase; indexing; lung cancer prevention; lung tumorigenesis; mouse model; oxidative DNA damage; prevent; programs; research study; selenoenzyme; tumor; urinary

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.

描述（由申请人提供）： 肺癌是美国癌症死亡的主要原因。肺癌发生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。流行病学和实验研究发现，膳食中的硒可以抑制多种癌症的发展。 1996 年的一项干预研究发现，食用硒补充剂的人患多种癌症的发病率较低，其中包括肺癌。然而，尚未建立动物模型表明膳食硒可抑制香烟烟雾诱发的肺癌。在这些研究中，我们建议在 A/J 小鼠模型中检验膳食硒可抑制香烟烟雾诱发肺癌的假设。将给小鼠喂食含有推荐水平的硒以及两种更高水平的硒的饮食，以确定补充硒是否会抑制肺部肿瘤的发生。在其他研究中，小鼠将在较短的时间内接触香烟烟雾，以确定膳食中的硒是否会抑制香烟烟雾诱导的细胞色素 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，则可以进一步研究该模型，以确定硒具有抑制作用的分子机制，从而为预防肺癌的可能饮食建议提供机制基础。

项目成果

Effect of dietary selenium and cigarette smoke on pulmonary cell proliferation in mice.

膳食硒和香烟烟雾对小鼠肺细胞增殖的影响。

• 发表时间: 2009-10
• 作者: Li, Jun;Tharappel, Job C;Han, Sung Gu;Cantor, Austin H;Lee, Eun Y;Gairola, C Gary;Glauert, Howard P
• 通讯作者: Glauert, Howard P

Dietary selenium fails to influence cigarette smoke-induced lung tumorigenesis in A/J mice.

膳食硒不能影响 A/J 小鼠香烟烟雾诱导的肺部肿瘤发生。

• 发表时间: 2013-06-28
• 影响因子: 9.7
• 作者: Glauert, Howard P;Martin, Joshua B;Li, Jun;Tharappel, Job C;Han, Sung Gu;Gillespie, Harold D;Cantor, Austin H;Lee, Eun Y;Gairola, C Gary
• 通讯作者: Gairola, C Gary