Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line
Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line
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DOI：
10.2307/3434505
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发表时间：
1999-03-01
影响因子：
10.4
通讯作者：
Pogo, BGT
中科院分区：
文献类型：
--
作者：
Go, V;Garey, J;Pogo, BGT
雌激素，无论是天然的还是合成的，都严重影响生殖发育、衰老和致癌。拟除虫菊酯类杀虫剂目前是室内虫害防治最广泛使用的药剂，有可能使人接触。以MCF-7人乳腺癌细胞系为实验对象，以pS2 mRNA水平为终点，研究了几种体外合成拟除虫菊酯类化合物的雌激素潜能。我们测试了氰菊酯、氰戊菊酯、d-反式丙烯菊酯和氯菊酯。纳摩尔浓度的磺胺菊酯或氰戊菊酯足以使pS2的表达略高于基础水平。在微摩尔浓度下，这两种拟除虫菊酯化合物诱导pS2表达的水平与10 nM 17 β -雌二醇诱导的水平相当（5倍）。磺胺菊酯与一种抗雌激素（ICI 164,384）联合治疗可消除雌激素活性，而氰戊酸与一种抗雌激素联合治疗的雌激素活性没有显著降低。此外，磺胺菊酯和氰戊酸均能诱导MCF-7细胞以剂量-反应方式增殖。氯菊酯和d-反式丙烯菊酯均不影响pS2的表达。氯菊酯在100 μ M浓度下对MCF-7细胞增殖有明显的影响，而d-反式乙酰丙菊酯在10 μ M浓度下对MCF-7细胞增殖有轻微的诱导作用，但在较高浓度下具有毒性。总的来说，我们的研究表明，每种拟除虫菊酯化合物在影响几种细胞途径方面都是独特的。这些发现表明，拟除虫菊酯应被视为激素干扰物，并应调查其对人类和野生动物内分泌功能的潜在影响。
Estrogens, whether natural or synthetic, dearly influence reproductive development, senescence, and carcinogenesis. Pyrethroid insecticides are now the most widely used agents for indoor pest control, providing potential for human exposure. Using the MCF-7 human breast carcinoma cell line, we studied the estrogenic potential of several synthetic pyrethroid compounds in vitro using pS2 mRNA levels as the end point. We tested sumithrin, fenvalerate, d-trans allethrin, and permethrin. Nanomolar concentrations of either sumithrin or fenvalerate were sufficient to increase pS2 expression slightly above basal levels. At micromolar concentrations, these two pyrethroid compounds induced pS2 expression to levels comparable to those elicited by 10 nM 17 beta-estradiol (five-fold). The estrogenic activity of sumithrin was abolished with co-treatment with an antiestrogen (ICI 164,384), whereas estrogenic activity of fenvalerate was not significantly diminished with antiestrogen co-treatment. In addition, both sumithrin and fenvalerate were able to induce cell proliferation of MCF-7 cells in a dose-response fashion. Neither permethrin nor d-trans allethrin affected pS2 expression. Permethrin had a noticeable effect on cell proliferation at 100 mu M, whereas d-trans allethrin slightly induced MCF-7 cell proliferation at 10 mu M, but was toxic at higher concentrations. Overall, our studies imply that each pyrethroid compound is unique in its ability to influence several cellular pathways. These findings suggest that pyrethroids should be considered to be hormone disrupters, and their potential to affect endocrine function in humans and wildlife should be investigated.