多氯联苯及其羟基化衍生物作为潜在外源性雌激素的评估：基于MCF-7细胞增殖和虹鳟鱼肝细胞原代培养中卵黄蛋白原诱导的体外研究。

Assessment of PCBs and hydroxylated PCBs as potential xenoestrogens: In vitro studies based on MCF-7 cell proliferation and induction of vitellogenin in primary culture of rainbow trout hepatocytes.

作者信息

Andersson P L, Blom A, Johannisson A, Pesonen M, Tysklind M, Berg A H, Olsson P E, Norrgren L

机构信息

Department of Environmental Chemistry, Umeå University, SE-901 87 Umeå, Sweden.

出版信息

Arch Environ Contam Toxicol. 1999 Aug;37(2):145-50. doi: 10.1007/s002449900499.

DOI:10.1007/s002449900499

PMID:10398763

Abstract

In the present study, four structurally diverse polychlorinated biphenyls (PCBs) were chosen from a set of 20 PCBs selected to represent the 154 tetra- through hepta-chlorinated biphenyls. The purpose was to determine estrogenic activities of the chosen PCBs and five of their hydroxylated derivatives (OH-PCBs). A human breast cancer cell line (MCF-7) and primary cultures of rainbow trout (Oncorhyncus mykiss) hepatocytes were used to determine estrogenic effects. The PCBs 2,2',4,6,6'-pentachlorobiphenyl (104) and 2,2',3, 4', 5,6,6'-heptachlorobiphenyl (188), and the hydroxylated PCBs 2,2', 4',6'-tetrachloro-4-biphenylol (4'-50), 2',4', 6'-trichloro-4-biphenylol (4'-30), 2',3,5, 5'-tetrachloro-4-biphenylol (4'-72), 2',3,3',5', 6'-pentachloro-4-biphenylol (4'-112), and 2',3,4',5, 6'-pentachloro-4-biphenylol (4'-121) significantly increased MCF-7 cell proliferation. The coaddition of hydroxytamoxifen, an estrogen antagonist, inhibited increased cell proliferation. The activity of the hydroxylated PCBs 4'-50 and 4'-30 was significantly higher at all nominal concentrations tested as compared to the corresponding PCB, viz., PCB 104. The hydroxylated PCBs 4'-50, 4'-30, 4'-72 and 4'-112 induced vitellogenin synthesis in rainbow trout hepatocytes. Significant differences were found in the MCF-7 system between the parent PCB and its hydroxylated derivative, viz., for 4'-50/4'-30 and 104, and in the rainbow trout hepatocyte assay between 4'-112 and 112, respectively. No activity was observed for PCB 58 in any of the two assays in the present study. Even though cells from two different species (human and fish) are used in the present study, the results obtained by the two methods agree fairly well. In both studies the hydroxylated PCBs were more active than the PCBs, and 4'-30 was the most active compound second only to 17beta-estradiol. http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p145.html

摘要

在本研究中，从一组20种多氯联苯（PCBs）中挑选出4种结构各异的多氯联苯，这20种多氯联苯被选来代表154种四氯至七氯联苯。目的是测定所选多氯联苯及其5种羟基化衍生物（OH-PCBs）的雌激素活性。使用人乳腺癌细胞系（MCF-7）和虹鳟（Oncorhyncus mykiss）肝细胞原代培养物来测定雌激素效应。多氯联苯2,2',4,6,6'-五氯联苯（104）和2,2',3,4',5,6,6'-七氯联苯（188），以及羟基化多氯联苯2,2',4',6'-四氯-4-联苯酚（4'-50）、2',4',6'-三氯-4-联苯酚（4'-30）、2',3,5,5'-四氯-4-联苯酚（4'-72）、2',3,3',5',6'-五氯-4-联苯酚（4'-112）和2',3,4',5,6'-五氯-4-联苯酚（4'-121）显著增加了MCF-7细胞增殖。雌激素拮抗剂羟基他莫昔芬的共同添加抑制了细胞增殖的增加。在所有测试的标称浓度下，羟基化多氯联苯4'-50和4'-30的活性显著高于相应的多氯联苯，即多氯联苯104。羟基化多氯联苯4'-50、4'-30、4'-72和4'-112诱导虹鳟肝细胞中卵黄蛋白原的合成。在MCF-7系统中，母体多氯联苯与其羟基化衍生物之间存在显著差异，即4'-50/4'-30与104之间，在虹鳟肝细胞试验中，4'-112与112之间也存在显著差异。在本研究的两种试验中，多氯联苯58均未观察到活性。尽管本研究中使用了来自两个不同物种（人类和鱼类）的细胞，但两种方法获得的结果相当吻合。在两项研究中，羟基化多氯联苯都比多氯联苯更具活性，4'-30是活性最高的化合物，仅次于17β-雌二醇。http://link.springer-ny.com/link/service/journals/00244/bibs/37n2p145.html