Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line

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.