SELENIUM CHEMOPREVENTION OF MAMMARY CARCINOGENESIS

硒化学预防乳腺癌

• 批准号: 3167777
• 负责人: CLEMENT C IP
• 金额: $ 16.56万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-04-01 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3167777
• 关键词: benzanthracenes; blood tests; breast neoplasms; butylated hydroxytoluene; cancer risk; carcinogenesis inhibitor; cellular oncology; chemical carcinogenesis; diet therapy; dietary lipid; dietary supplements; dietary trace element; disease /disorder model; fluorimetry; gel electrophoresis; glutathione peroxidase; methionine; nutrition related tag; peroxidation; selenium; stainings; tissue /cell preparation; tocopherols

The objective of this proposal is to continue studies on the anticarcinogenic action of selenium using the dimethylbenz(a)anthracene (DMBA)-induced mammary tumor model in female SD rats. The theme will be focused on the interaction between selenium and other dietary factors in the modification of mammary cancer risk. Our ultimate goal is to define a set of guidelines which optimizes the prophylactic action of selenium. In addition, we are also interested in delineating the mechanism(s) of action by which selenium inhibits tumorigenesis. Aim 1 is designed to study the interaction of selenium and vitamin E in cancer chemoprevention. Our strategy is to complete a comprehensive set of dose response experiments in the quantitative analysis of the proposed synergisms between selenium (both selenite and selenomethionine) and vitamin E in protection against mammary tumorigenesis. The kinetics of vitamin E accumulation in tissues will also be studied under these conditions. Aim 2 is designed to study the effects of protein and methionine intake on the anticarcinogenic efficacy of selenium. The basis for this study is to determine how the nutritional status of the host can affect the effectiveness of selenium in protection against cancer. Methionine is intimately involved in the metabolic fates of both selenite and selenomethionine. Consequently, methionine can exert an effect that is independent of the total protein intake. We also plan to follow up our previous observation on glutathione metabolism, specifically targeting our effort on changes of tissue GSH and GSSG levels as influenced by protein, methionine and selenium intake. Aim 3 is designed to study the effect of selenium supplemenation on tissue selenium levels and the metabolism of selenium. The purpose of this study is to test the significance of tissue selenium level as predictor of chemopreventive effectiveness. The quantitative analysis of low molecular weight selenium metabolites will be addressed in this aim. Aim 4 is designed to study the incorporation of selenium into selenoproteins as analyzed by two-dimensional gel electrophoresis. Changes in the expression of these proteins may be important in the chemopreventive action of selenium and the sensitivity to selenium inhibition of cellular proliferation.

该提议的目的是继续研究 使用二甲基苯子（a）蒽的抗癌作用 （DMBA）在雌性SD大鼠中诱导的乳腺肿瘤模型。 主题将是 专注于硒与其他饮食因素之间的相互作用 乳腺癌风险的改变。 我们的最终目标是定义 一组指南，可优化硒的预防作用。 在 此外，我们也有兴趣描述动作的机制 硒抑制肿瘤发生。 AIM 1旨在研究 硒和维生素E在癌症化学预防中的相互作用。 我们的 策略是完成一组全面的剂量反应实验 对硒之间提出的协同作用的定量分析（均 硒酸盐和硒甲氨酸）和维生素E可防止乳腺 肿瘤发生。 维生素E在组织中积累的动力学也将 在这些条件下进行研究。 AIM 2旨在研究效果 蛋白质和蛋氨酸在抗癌功效上的摄入量 硒。 这项研究的基础是确定营养 宿主的状态会影响硒在保护方面的有效性 反对癌症。 蛋氨酸与代谢命运密切相关 硒石和硒蛋白。 因此，蛋氨酸可以施加 与总蛋白质摄入无关的作用。 我们还计划 跟进我们先前对谷胱甘肽代谢的观察，特别是 针对受影响 通过蛋白质，蛋氨酸和硒摄入量。 AIM 3旨在研究 硒补给对组织硒水平和 硒的代谢。 这项研究的目的是测试 组织硒水平的重要性作为化学预防的预测指标 效力。 低分子量硒的定量分析 代谢物将在此目标中解决。 AIM 4旨在研究 将硒掺入硒蛋白中 二维凝胶电泳。 这些表达的变化 蛋白质在硒的化学预防作用中可能很重要 对硒抑制细胞增殖的敏感性。