In vitro evaluation of uranium estrogenicity

描述(申请人提供)：1940-1980年间，在纳瓦霍保留地进行了重铀(U)开采。纳瓦霍矿工没有被告知与铀矿开采有关的健康风险，因此没有采取预防措施保护他们自己或他们的家人。1000多个煤矿没有妥善关闭，有可能导致继续暴露。许多纳瓦霍人患有被认为是由于接触U而患上的疾病。最值得注意的是，居住在铀矿附近的纳瓦霍女孩的性腺、生殖细胞和生殖器癌的发病率要高出17倍。许多重金属是雌激素；然而，U还没有被检测。初步数据显示，U能刺激MCF-7乳腺癌细胞增殖，并能增加去卵巢小鼠的子宫重量。U在体外模拟17-雌二醇以引发雌激素敏感反应的假设将得到验证。在体外，将通过雌激素受体结合试验和MCF-7细胞增殖来检测铀的雌激素活性。此外，U和ER的相互作用将通过EM和共聚焦显微镜可视化。

DESCRIPTION (provided by applicant): During 1940-1980s, heavy uranium (U) mining took place on the Navajo Reservation. Navajo miners were not informed of health risks associated with U mining, thus did not take precautions to protect themselves or their families. More than 1000 mines were not properly closed, potentially leading to continued exposure. Many Navajos suffer from maladies thought to be from U exposure. Most notable is a 17 times greater incidence of gonadal, germ cell, and genital cancer in Navajo girls who lived near U mining. Many heavy metals are estrogenic; however, U has not been examined. Preliminary data demonstrate U stimulation of MCF-7 breast cancer cell proliferation and an increase in uterine weight in U treated ovariectomized mice. The hypothesis that U mimics 17-estradiol in vitro to elicit estrogen-sensitive responses will be tested. In vitro estrogenicity of uranium will be examined in an estrogen receptor binding assay and MCF-7 cell proliferation. Additionally, U and ER interaction will be visualized by EM and confocal microscopy.