MAMMARY CHEMOPREVENTION--HORMONES/VITAMIN A/SELENIUM

本提案的总体目标是评估以下概念 低剂量的不同微量营养素一起使用可能更有效 高剂量单一微量营养素和复合微量营养素 与激素因素的相互作用可能会改善化学预防活性 因为它们可能有不同的作用机制。致癌的原因 乳腺的独特之处在于它有两种截然不同的癌症， 荷尔蒙依赖和独立。使用不同类别的代理 (即，每个可能特定于发生的癌症类型)将 似乎是预防乳腺癌的合理方法。使用这个 理论基础，建议进行研究以评估其对乳腺癌的影响。 防止激素、视黄酸乙酯和硒联合治疗。 如果这些药剂发生相当大的重叠，将是可取的。 (例如，视黄酸乙酯被认为能有效地预防这两种激素 依赖癌症和独立癌症)。 拟议的实验将使用甲基亚硝脲(MNU)诱导的 雌性SD大鼠乳腺癌模型的建立。化学预防 使用的药物将是短期的、高剂量的雌激素加黄体酮，以及 低剂量的视黄酸乙酯和亚硒酸钠。尽管这是一个重大的努力 每项研究的目的是确定这些药物在预防 乳腺癌综合治疗可能出现的毒副作用也会 经过广泛调查。许多种类的化合物已经被证明是 具有化学预防活性，但它们的毒性使其临床无法使用 使用。这些专门的研究旨在开发化学预防 这两种策略都将降低乳腺的敏感性 致癌物(即防止发病)和防止进展 和/或促进启动的细胞转化为直肠癌。决赛 给出的实验将决定组合的效果 激素、视黄酸乙酯和硒对生殖和哺乳的影响 性能。如果乳腺癌的化学预防要在一个 年轻人，使用的试剂不能干扰这些 生理功能。

The overall objectives of this proposal are to evaluate the concepts that low doses of different micronutrients used together may be more effective than high doses of a single micronutrient and that combining micronutrient interaction with hormonal factors may improve chemopreventive activity since they probably have different mechanisms of action. Carcinogenesis of the mammary gland is unique in that two distinct types of cancers occur, hormone dependent and independent. The use of different classes of agents (i.e., each perhaps specific for the type of cancers that occur) would appear to be a reasonable approach to preventing breast cancer. Using this rationale, studies are proposed to evaluate the effect on mammary cancer prevention of combining hormone, retinyl acetate and selenium treatments. It would be desirable if considerable overlap of these agents occurred (e.g. retinyl acetate is thought to be effective in preventing both hormone dependent and independent cancers). The proposed experiments will use the methylnitrosourea (MNU)-induced mammary cancer model in female Sprague-Dawley rats. The chemopreventive agents used will be short-term, high-dose estrogen plus progesterone, and low doses of retinyl acetate and sodium selenite. Although a major effort of each study is to determine the effect of the agents on prevention of mammary cancers, the possible toxicity of combining treatments will also be extensively investigated. Many classes of compounds have been shown to have chemopreventive activity, but their toxicity precludes their clinical use. The specific studies are designed to develop chemopreventive strategies that will both decrease the susceptibility of the mammary gland to carcinogens (i.e., prevent initiation) and prevent the progression and/or promotion of initiated cells to frank carcinomas. A final experiment is presented that will determine the effect of combining hormones, retinyl acetate, and selenium on reproductive and lactational performance. If chemoprevention of breast cancer is to be advocated in a young population, the agents used must not interfere with these physiological functions.