Examination of the estrogenicity of 2,4,6,2',6'-pentachlorobiphenyl (PCB 104), its hydroxylated metabolite 2,4,6,2',6'-pentachloro-4-biphenylol (HO-PCB 104), and a further chlorinated derivative, 2,4,6,2',4',6'-hexachlorobiphenyl (PCB 155).
Examination of the estrogenicity of 2,4,6,2',6'-pentachlorobiphenyl (PCB 104), its hydroxylated metabolite 2,4,6,2',6'-pentachloro-4-biphenylol (HO-PCB 104), and a further chlorinated derivative, 2,4,6,2',4',6'-hexachlorobiphenyl (PCB 155).
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DOI：
10.1289/ehp.971051238
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发表时间：
1997-11
影响因子：
10.4
通讯作者：
Zacharewski TR
中科院分区：
文献类型：
--
作者：
Fielden MR;Chen I;Chittim B;Safe SH;Zacharewski TR
几项研究报告称，多氯联苯（PCB）表现出雌激素活性;然而，尚不清楚这些反应是否与多氯代烃或其羟基化代谢物有关。为了进一步验证这一假设，采用一系列体内、体外试验研究了2，4，6，2 '，6'-五氯联苯（PCB 104）及其对羟基化衍生物2，4，6，2 '，6'-五氯-4-联苯醇（PCB 104）的雌激素样和抗雌激素样活性（HO-PCB 104）及其对位氯化衍生物2，4，6，2 '，4'，6 '-六氯联苯（PCB 155）。发现PCB 104 1）与氚化17 β-雌二醇（E2）竞争结合小鼠子宫雌激素受体（ER）; 2）在用Gal 4-人ER嵌合构建体瞬时转染的MCF-7人乳腺癌细胞中诱导基因表达Gal 4-HEGO）和Gal 4调节的荧光素酶报告基因（17 m5-G-Luc）;和3）以剂量依赖性方式增加MCF-7细胞增殖。HO-PCB 104在体外试验中表现出比PCB 104更大的雌激素活性。然而，对用PCB 104孵育的MCF-7细胞制备的提取物进行气相色谱-质谱分光光度分析，未能检测到预期主要代谢产物HO-PCB 104的存在。与PCB 104和HO-PCB 104相比，对氯代衍生物PCB 155的雌激素活性最小，但在与1 nM E2共同处理后，它确实表现出显著的抗雌激素活性。与单独的E2相比，PCB 104与1 nM E2的共处理对报告基因表达没有影响，而10 μ M HO-PCB 104与1 nM E2显示出加和性。在202 mg/kg剂量下，PCB 104以剂量依赖性方式增加卵巢切除CD-1小鼠的子宫湿重，并在202、16和1.7 mg/kg剂量下诱导阴道上皮细胞角化。这些研究表明，除了羟基化代谢物外，某些母体多氯联苯同系物也可能表现出雌激素和抗雌激素活性。
Several studies have reported that polychlorinated biphenyls (PCBs) exhibit estrogenic activity; however, it is not clear if these responses are associated with the polychlorinated hydrocarbon or its hydroxylated metabolite. In order to further test this hypothesis, a battery of in vitro and in vivo assays were used to investigate the estrogenic and antiestrogenic activities of 2,4,6,2',6'-pentachlorobiphenyl (PCB 104), its para-hydroxylated derivative 2,4,6,2',6'-pentachloro-4-biphenylol (HO-PCB 104), and its para-chlorinated derivative 2,4,6,2',4',6'-hexachlorobiphenyl (PCB 155). PCB 104 was found to 1) compete with tritiated 17beta-estradiol (E2) for binding to the mouse uterine estrogen receptor (ER); 2) induce gene expression in MCF-7 human breast cancer cells transiently transfected with the Gal4-human ER chimeric construct (Gal4-HEGO) and the Gal4-regulated luciferase reporter gene (17m5-G-Luc); and 3) increase MCF-7 cell proliferation in a dose-dependent manner. HO-PCB 104 exhibited greater estrogenic activity than PCB 104 in the in vitro assays examined. However, gas chromatographic-mass spectrophotometric analysis of extracts prepared from MCF-7 cells incubated with PCB 104 failed to detect the presence of the expected major metabolite HO-PCB 104. The estrogenic activity of the para-chlorinated derivative, PCB 155, was minimal compared to PCB 104 and HO-PCB 104, but it did exhibit significant antiestrogenic activity following co-treatment with 1 nM E2. Co-treatment of PCB 104 with 1 nM E2 had no effect on reporter gene expression compared to E2 alone, while 10 microM HO-PCB 104 exhibited additivity with 1 nM E2. At a dose of 202 mg/kg,PCB 104 increased uterine wet weight in ovariectomized CD-1 mice and induced vaginal epithelial cell cornification at 202, 16, and 1.7 mg/kg in a dose-dependent manner. These studies demonstrate that in addition to the hydroxylated metabolites, selected parent PCB congeners may also exhibit estrogenic and antiestrogenic activities.
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影响因子：
2.1
作者：
Balaguer, P;Joyeux, A;Zacharewski, T
通讯作者：
Zacharewski, T
影响因子：
4.1
作者：
BOKENKAMP, D;JUNGBLUT, PW;THOLE, HH
通讯作者：
THOLE, HH
影响因子：
4.8
作者：
ANDERSON, JN;PECK, EJ;CLARK, JH
通讯作者：
CLARK, JH
影响因子：
56.9
作者：
EVANS, RM
通讯作者：
EVANS, RM
影响因子：
5.1
作者：
BROUWER, A;BLANER, WS;VANDENBERG, KJ
通讯作者：
VANDENBERG, KJ