MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

• 批准号: 2384485
• 负责人: SAMUEL WYLLIE
• 金额: $ 1.39万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-11-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2384485
• 关键词: MINORITY; PREDOCTORAL; FELLOWSHIP; PROGRAM

In this project, the role of Fe will be examined in the generation of reactive hydroxy radicals by redox-cycling of estrogens and its role in estrogen-induced carcinogenesis. In westernized societies, excess iron is taken in via dietary supplements. However, an elevated risk of cancer is associated in humans with high body iron stores. The hypothesis is that superoxide radicals, generated by metabolic redox cycling of catecholestrogen metabolites, reduce Fe3+, stored in ferritin, to Fe2+ which is released from ferritin and in turn reduces H2O2 to OH (Fenton reaction). The goal of this study is to demonstrate that iron is mobilized from ferritin during metabolic redox cycling of estrogens and that it supports hydroxy radical generation and DNA damage during estrogen-induced carcinogenesis. This hypothesis will be tested by examining 1. release of Fe2+ from ferritin/Fe3+ by redox cycling of estrogens in vitro. 2. the possible accumulation of chelatable Fe2+ in kidney of estrogen-treated hamsters prior to the appearance of renal tumors, but not in liver in which tumors are not induced by this treatment. 3. Fe2+ release in kidney of estrogen-treated hamsters as a redox cycling-dependent process (by using inhibitors of cytochrome P450) and not a receptor-mediated process (by using antiestrogens) 4. the incidence of estrogen-induced kidney tumors in hamsters treated with estradiol and diets containing very low, medium or high levels of iron.

在这个项目中，铁的作用将被检查在产生 雌激素氧化还原循环产生的活性羟基自由基及其在 雌激素诱导的致癌作用。在西方社会，过量的铁 是通过膳食补充剂摄入的然而，患癌症的风险增加 在人体内与体内高铁储存有关。这个假设是 超氧化物自由基，由代谢氧化还原循环产生， 儿茶素雌激素代谢产物，将储存在铁蛋白中的Fe 3+还原为Fe 2 + 从铁蛋白中释放出来，然后将H2 O2还原为OH（芬顿 反应）。这项研究的目的是证明铁是 在雌激素的代谢氧化还原循环过程中从铁蛋白动员， 它支持羟基自由基的产生和DNA损伤， 雌激素诱导的致癌作用。这一假设将由以下人员进行检验： 检查1.通过氧化还原循环从铁蛋白/Fe 3+释放Fe 2 + 体外雌激素。 2.可螯合Fe ~（2+）在 雌激素处理的仓鼠的肾脏在肾脏出现之前 肿瘤，但不是在肝脏中，其中肿瘤不是由这种 治疗 3.雌激素处理的仓鼠肾脏中Fe ~（2+）的释放 氧化还原循环依赖性过程（通过使用细胞色素P450的抑制剂） 而不是受体介导的过程（通过使用抗雌激素） 4.的 雌激素诱导的仓鼠肾肿瘤的发生率 雌二醇和含有非常低、中或高水平铁的饮食。