Relationship between the results of in vitro receptor binding assay to human estrogen receptor α and in vivo uterotrophic assay:: Comparative study with 65 selected chemicals
Relationship between the results of in vitro receptor binding assay to human estrogen receptor α and in vivo uterotrophic assay:: Comparative study with 65 selected chemicals
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DOI：
10.1016/j.tiv.2007.08.004
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发表时间：
2008-02-01
影响因子：
3.2
通讯作者：
Ohtaki, Masahiro
中科院分区：
文献类型：
--
作者：
Akahori, Yumi;Nakai, Makoto;Ohtaki, Masahiro
为了筛选具有内分泌干扰能力的化学物质，在 OECD 测试框架中，子宫营养测定法被置于比 ER 结合测定法更高的水平，以检测 ER 介导的活性。然而，没有研究可以证明这些测定之间存在明确的关系。为了阐明体外 ER 结合和体内子宫营养测定之间的关系，并确定 ER 结合测定有意义的结合效力，我们比较了涵盖各种化学品类别的 65 种化学品的这些测定结果。在 logRBA（相对结合亲和力）和 logLED（最低有效剂量）之间的定量比较下，log RBA 与雌激素和抗雌激素化合物的 logLED 均具有良好的相关性，分别为 r(2) = 0.67 (n = 28) 和 0.79 (n = 23)。发现0.00233%的RBA是子宫营养测定中引发雌激素或抗雌激素活性的最低ER结合效力，因此该值被认为是子宫营养测定中雌激素或抗雌激素活性的检测限。使用该值作为截止值提供了最佳的一致性率 (82%)。这些发现可用于采用分层方法来识别可能在体内诱导 ER 介导作用的化学物质。 (c) 2007 Elsevier Ltd. 保留所有权利。
For screening chemicals possessing endocrine disrupting potencies, the uterotrophic assay has been placed in a higher level in the OECD testing framework than the ER binding assay to detect ER-mediated activities. However, there are no studies that can demonstrate a clear relationship between these assays. In order to clarify the relationship between the in vitro ER binding and in vivo uterotrophic assays and to determine meaningful binding potency from the ER binding assay, we compared the results from these assays for 65 chemicals spanning a variety of chemicals classes. Under the quantitative comparison between logRBAs (relative binding affinities) and logLEDs (lowest effective doses), the log RBA was well correlated with both logLEDs of estrogenic and anti-estrogenic compounds at r(2) = 0.67 (n = 28) and 0.79 (n = 23), respectively. The RBA of 0.00233% was found to be the lowest ER binding potency to elicit estrogenic or anti-estrogenic activities in the uterotrophic assay, accordingly this value is considered as the detection limit of estrogenic or anti-estrogenic activities in the uterotrophic assay. The usage of this value as cutoff provided the best concordance rate (82%). These findings are useful in a tiered approach for identifying chemicals that have potential to induce ER-mediated effects in vivo. (c) 2007 Elsevier Ltd. All rights reserved.