In vitro evaluation of uranium estrogenicity

描述（由申请人提供）：在1940年至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开采有关的健康风险，因此没有采取预防措施保护自己或家人。超过1000个地雷没有完全关闭，可能导致持续暴露。许多纳瓦霍人患有被认为是由于暴露在辐射中而导致的疾病。最值得注意的是，居住在铀矿附近的纳瓦霍族女孩患性腺癌、生殖细胞癌和生殖器官癌的几率要高出17倍。许多重金属是雌激素；然而，U还没有被检查过。初步数据表明，U可刺激MCF-7乳腺癌细胞增殖，并使经U处理的去卵巢小鼠的子宫重量增加。U在体外模拟17-雌二醇以引起雌激素敏感反应的假设将得到验证。通过雌激素受体结合试验和MCF-7细胞增殖试验来检测铀的体外雌激素原性。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.