Interlaboratory comparison of four in vitro assays for assessing androgenic and antiandrogenic activity of environmental chemicals.
Interlaboratory comparison of four in vitro assays for assessing androgenic and antiandrogenic activity of environmental chemicals.
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DOI：
10.1289/ehp.112-1241964
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发表时间：
2004-05
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
--
作者：
在一项国际实验室间研究中，我们评估并比较了四种体外检测雄激素激动剂和拮抗剂的方法。实验室1用稳定转染人雄激素受体的人乳腺癌细胞进行细胞增殖试验（试验1）。其他实验室使用报告基因检测，其中两个基于稳定转染的人前列腺癌细胞（实验2）或人乳腺癌细胞（实验4），第三个基于瞬时转染的中国仓鼠卵巢细胞（实验3）。四个实验室收到了四种编码化合物和两种对照：两种甾体雄激素，两种抗雄激素，一种雄激素对照，5 -二氢睾酮（DHT），一种抗雄激素对照，比卡鲁胺（ICI 176,334）。4-雄烯酮-3、17-二酮和17-甲基睾酮的雄激素活性均正确检测。对于这两种化合物，相对于阳性对照（RAPs）计算的雄激素潜能保持在一个数量级以内。然而，实验室3计算出4-雄烯酮-3,17-二酮的RAP高出50倍。所有试验均检测并量化了vinclozolin的抗雄激素作用[中位抑制浓度（IC50）值为1.1倍符号10(-7)M至4.7倍符号10(-7)M]。在试验2和3中，vinclozolin在测试的最高浓度下显示出部分雄激素活性。对于vinclozolin，计算出的相对于比卡鲁胺的抗雄激素潜能（RAAPs）相差不超过10倍，IC50值与比卡鲁胺相匹配。同样，我们发现三-（4-氯苯基）甲醇具有抗雄激素活性。RAAP值在0.086 ~ 0.37之间。三项试验显示该化合物的细胞毒性在1倍符号10(-5)m以上。总之，所有试验都证明了敏感的筛选工具可以准确地检测和量化雄激素受体介导的这些化学物质的雄激素和抗雄激素作用，变异系数在8%到90%之间。
We evaluated and compared four in vitro assays to detect androgen agonists and antagonists in an international interlaboratory study. Laboratory 1 used a cell proliferation assay (assay 1) with human mammary carcinoma cells stably transfected with human androgen receptor. The other laboratories used reporter gene assays, two based on stably transfected human prostate carcinoma cells (assay 2) or human mammary carcinoma cells (assay 4), and the third based on transient transfection of Chinese hamster ovary cells (assay 3). Four laboratories received four coded compounds and two controls: two steroidal androgens, two antiandrogens, an androgenic control, 5alpha-dihydrotestosterone (DHT), and an antiandrogenic control, bicalutamide (ICI 176,334). All laboratories correctly detected the androgenic activity of 4-androsten-3,17-dione and 17alpha-methyltestosterone. For both compounds, the calculated androgenic potencies relative to the positive control (RAPs) remained within one order of magnitude. However, laboratory 3 calculated a 50-fold higher RAP for 4-androsten-3,17-dione. All assays detected and quantified the antiandrogenic effect of vinclozolin [median inhibitory concentration (IC50) values ranging from 1.1 times symbol 10(-7) M to 4.7 times symbol 10(-7) M]. In assays 2 and 3, vinclozolin showed partial androgenic activity at the highest concentrations tested. For vinclozolin, calculated antiandrogenic potencies relative to bicalutamide (RAAPs) differed no more than a factor of 10, and IC50 values matched those of bicalutamide. Similarly, we found antiandrogenic activity for tris-(4-chlorophenyl)methanol. RAAP values were between 0.086 and 0.37. Three assays showed cytotoxicity for this compound at or above 1 times symbol 10(-5) M. In summary, all assays proved sensitive screening tools to detect and quantify androgen receptor-mediated androgenic and antiandrogenic effects of these chemicals accurately, with coefficients of variation between 8 and 90%.
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DOI：
10.1016/0022-4731(87)90303-7
发表时间：
1987-01-01
影响因子：
4.1
作者：
CHANG, CS;LIAO, ST
通讯作者：
LIAO, ST
影响因子：
8.8
作者：
Korner, W;Hanf, V;Hagenmaier, H
通讯作者：
Hagenmaier, H
影响因子：
3.8
作者：
COOK, JC;MULLIN, LS;BIEGEL, LB
通讯作者：
BIEGEL, LB
DOI：
10.1006/bbrc.1998.8209
发表时间：
1998-03-06
影响因子：
3.1
作者：
Dalton, JT;Mukherjee, A;Miller, DD
通讯作者：
Miller, DD
DOI：
10.1016/0022-4731(90)90248-q
发表时间：
1990-03-01
影响因子：
4.1
作者：
EIL, C;NISULA, BC
通讯作者：
NISULA, BC