Go V, Garey J, Wolff M S, Pogo B G
Molecular Basis of Diseases Program, Division of Neoplastic Diseases, Mount Sinai School of Medicine, New York, NY 10029 USA.
Environ Health Perspect. 1999 Mar;107(3):173-7. doi: 10.1289/ehp.99107173.
Estrogens, whether natural or synthetic, clearly 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 17ss-estradiol (fivefold). 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 microM, whereas d-trans allethrin slightly induced MCF-7 cell proliferation at 10 microM, 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 disruptors, and their potential to affect endocrine function in humans and wildlife should be investigated.
雌激素,无论天然的还是合成的,都对生殖发育、衰老和致癌作用有显著影响。拟除虫菊酯类杀虫剂是目前室内害虫防治中使用最广泛的药剂,这使得人类有接触它们的潜在风险。我们使用MCF-7人乳腺癌细胞系,以pS2 mRNA水平为终点,在体外研究了几种合成拟除虫菊酯化合物的雌激素活性。我们测试了氯菊酯、氰戊菊酯、右旋烯丙菊酯和顺式氯氰菊酯。纳摩尔浓度的氯菊酯或氰戊菊酯足以使pS2表达量比基础水平略有增加。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 17β-雌二醇诱导的水平相当(高出五倍)。氯菊酯与抗雌激素(ICI 164,384)共同处理时,其雌激素活性被消除,而氰戊菊酯与抗雌激素共同处理时,其雌激素活性没有显著降低。此外,氯菊酯和氰戊菊酯都能够以剂量反应方式诱导MCF-7细胞增殖。顺式氯氰菊酯和右旋烯丙菊酯均未影响pS2表达。顺式氯氰菊酯在100 microM时对细胞增殖有显著影响,而右旋烯丙菊酯在10 microM时轻微诱导MCF-7细胞增殖,但在较高浓度时具有毒性。总体而言,我们的研究表明,每种拟除虫菊酯化合物影响多种细胞途径的能力是独特的。这些发现表明,拟除虫菊酯应被视为激素干扰物,其对人类和野生动物内分泌功能的潜在影响值得研究。