Application of an androgen receptor assay for the characterisation of the androgenic or antiandrogenic activity of various phenylurea herbicides and their derivatives
Application of an androgen receptor assay for the characterisation of the androgenic or antiandrogenic activity of various phenylurea herbicides and their derivatives
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DOI：
10.1039/a804606i
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发表时间：
1998-12-01
期刊：
影响因子：
4.2
通讯作者：
Sauerwein, H
中科院分区：
文献类型：
--
作者：
Bauer, ERS;Meyer, HHD;Sauerwein, H
测试了不同物质从牛雄激素受体置换[H-3]二氢睾酮（[H-3]DHT）的效力。在沉积物和表面沃茨中发现的苯基脲除草剂利谷隆及其衍生物3，4-二氯苯胺（3，4-DCA），已知可取代大鼠雄激素受体中的结合睾酮。由于3，4-DCA被鱼类迅速吸收并代谢成3，4-二氯乙酰苯胺（3，4-DCAc），因此研究了置换效应是归因于3，4-DCA还是归因于3，4-DCAc。将3，4-DCAc雄激素受体结合的效力与几种苯基脲类化合物进行了比较。在以小牛子宫胞液为雄激素受体制剂的放射受体测定中，内源性配体[3 H]DHT的特异性结合完全被增加浓度的3，4-DCAc所取代。各种化合物的相对结合亲和力（RBA）约为DHT的1/10（4）和1/10（5）。其中，3，4-DCA的亲和力最高（1.31 × 10 ~（-4）），其次是利谷隆、3，4-二氯苯脲、氟草胺、3，4-DCA和敌草隆，RBA最低（2.4 × 10 ~（-5））。因此，必须考虑异生物质化合物的代谢，以估计潜在的生态毒理学效应。该试验不仅可用于筛选与环境相关的样品（如地表沃茨）中的雄激素和抗雄激素样物质，还可用于药物检测和残留监测。
The potency of different substances for [H-3]dihydrotestosteone ([H-3]DHT) displacement from the bovine androgen receptor was tested. The phenylurea herbicide linuron and its derivative 3,4-dichloroaniline (3,4-DCA), which are found in sediments and surface waters, are known to displace bound testosterone from the rat androgen receptor. Because 3,4-DCA is rapidly taken up by fish and metabolised into 3,4-dichloroacetanilide (3,4-DCAc), it was investigated whether the displacement effects are attributable to 3,4-DCA or to 3,4-DCAc. The potency of 3,4-DCAc androgen receptor binding was compared with that of several phenylurea compounds. Ln a radioreceptor assay with calf uterus cytosol as androgen receptor preparation, the specific binding of [3H]DHT, the endogenous ligand, was completely displaceable by increasing concentrations of 3,4-DCAc. The relative binding affinities (RBA) of the various compounds were about 1/10(4) tp 1/10(5) of that of DHT. 3,4-DCAc had the relative highest affinity (1.31 x 10(-4)), followed by linuron, 3,4-dichlorophenylurea, flutamide, 3,4-DCA and diuron with the lowest RBA (2.4 x 10(-5)). Hence the metabolism of xenobiotic compounds has to be considered to estimate potential ecotoxiocological effects. This test not only can be used to screen for androgen- and antiandrogen-like substances in environmentally relevant samples such as surface waters, but might also be applied for drug testing and for residue monitoring.