Estrogenic activity of uranium in vitro and in vivo

铀的体外和体内雌激素活性

基本信息

批准号：
7120248
负责人：
CHERYL A DYER
金额：
$ 4.42万
依托单位：
NORTHERN ARIZONA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-02-15 至 2007-02-14
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Uranium toxicity has been analyzed primarily by investigating its radioactive properties. However as the densest naturally occurring element it also exerts chemical toxicity like other heavy metals. We have been investigating the reproductive chemical toxicity of uranium in female mice. In vivo exposure of mice to uranyl nitrate in their drinking water results in the selective significant reduction in only primary follicles in the ovary and increased uterine weight. These outcomes are typical estrogenic responses. To assess putative estrogenicity of uranium we used the estrogen sensitive Mcf-7 breast cancer cell E-Screen bioassay and preliminary data suggests that uranium, similar to many other heavy metals, is estrogenic. Here we propose to further characterize the putative estrogenicity of uranium. Our working hypothesis is that uranium stimulates estrogenic responses in vitro and in vivo via estrogen receptor alpha, which will be tested in 2 specific aims: 1) Use the Mcf-7 cell E-Screen assay to analyze uranium's estrogenic potency, receptor specificity and effective concentration, culture ovarian theca/interstitial cells to examine the impact of uranium on androgen production; 2) Conduct in vivo experiments in intact and ovariectomized mice to assess uranium's impact on reproductive organs and endocrine measures. NAU is located on the southwest perimeter of the Navajo Nation where until the early1990's there was active uranium mining. Unremediated mines and ore processing sites have contaminated drinking water sources with uranium at ppb to ppm levels. Data is very limited but shows that reproductive cancers in Navajo teenage girls are 17 times more frequent than in age-matched U.S. teenagers. Our long range goal is to address if it is possible that chronic consumption of uranium-contaminated water and/or in utero exposure, similar to the effect of diethylstilbestrol exposure in utero, has contributed to the exceedingly high incidence of genital and reproductive cancers in Navajo teenagers by investigating in our laboratory the putative estrogenicity of uranium in vitro and in vivo.

描述（由申请人提供）：铀毒性主要是通过研究其放射性特性来分析的。但是，作为最自然发生的元素，它也像其他重金属一样施加化学毒性。我们一直在研究铀在雌性小鼠中的生殖化学毒性。小鼠在饮用水中对硝酸铀酰的体内暴露导致卵巢中原发性卵泡的选择性显着降低，并增加了子宫体重。这些结果是典型的雌激素反应。为了评估铀的推定雌激素，我们使用了雌激素敏感的MCF-7乳腺癌细胞电子屏幕生物测定和初步数据表明，与许多其他重金属类似的铀具有雌激素。在这里，我们建议进一步表征铀的假定雌激素。 Our working hypothesis is that uranium stimulates estrogenic responses in vitro and in vivo via estrogen receptor alpha, which will be tested in 2 specific aims: 1) Use the Mcf-7 cell E-Screen assay to analyze uranium's estrogenic potency, receptor specificity and effective concentration, culture ovarian theca/interstitial cells to examine the impact of uranium on androgen production; 2）在完整和卵巢切除小鼠中进行体内实验，以评估铀对生殖器官和内分泌措施的影响。 NAU位于Navajo Nation的西南周围，直到1990年代初，有活跃的铀开采。未散发的矿山和矿石加工地点在PPB时以铀为污染了饮用水源，至PPM水平。数据非常有限，但表明纳瓦霍少女的生殖癌的频率是年龄匹配的美国少年的17倍。 Our long range goal is to address if it is possible that chronic consumption of uranium-contaminated water and/or in utero exposure, similar to the effect of diethylstilbestrol exposure in utero, has contributed to the exceedingly high incidence of genital and reproductive cancers in Navajo teenagers by investigating in our laboratory the putative estrogenicity of uranium in vitro and in vivo.