Abstract
Typical environmental endocrine-disrupting chemicals (EDCs) such as estradiol valerate (EV), diethylstilbestrol (DES), di-2-ethylhexyl phthalate (DEHP), mono-2-ethylhexyl phthalate (MEHP), and bisphenol A (BPA) have a strong reproductive and developmental toxicity at low concentrations. However, information on their joint toxicity is scarce. In this study, we evaluated the combined effects of EV and other four EDCs (DES, DEHP, MEHP, and BPA) on the human breast MCF-7 cells by detecting the cell proliferation, intracellular reactive oxygen species (ROS) levels, and estrogen receptor alpha (ERα) protein expression using equal concentration ratio method. The results showed that, after exposure for 24, 48, and 72 h, single EV, DES, and BPA can promote the proliferation of MCF-7 human breast cancer cells, and EV has the strongest effect in inducing cell proliferation. DEHP and MEHP cannot induce MCF-7 cell proliferation for all exposure time, while cell proliferation induced by EV was significantly attenuated by DES, BPA, DEHP, and MEHP when they mixed with EV. For intracellular ROS, single EV, BPA, DES, DEHP, and MEHP elevated intracellular ROS levels for different exposure time. Similar to the cell proliferation, DES and BPA decreased intracellular ROS levels induced by EV when they mixed with EV for 24 h. EV, DES, and BPA exposed alone or combined with EV upregulated the ERα protein expression. However, DEHP and MEHP exposed alone or combined with EV had no effect on ERα protein expression, indicating that DEHP or MEHP could attenuate ERα protein expression upregulated by EV. These results showed that the joint toxicity of binary mixtures of EV and other EDCs do not interact in a synergistic fashion in inducing cell proliferation, intracellular ROS levels, and ERα protein expression. These findings have important implications in the human risk assessments of EV mixed with other EDCs in the environment.
Highlights
Environmental endocrine-disrupting chemicals (EDCs) such as estradiol valerate (EV), diethylstilbestrol (DES), bisphenol A (BPA), diethylhexyl phthalate (DEHP), and mono-2-ethylhexyl phthalate (MEHP) bring up prevalent attention because they have a strong reproductive and developmental toxicity on human and various animal species at low doses [1, 2].EV is one of the most common sources of free E2 in hormone replacement therapy [3]
After MCF-7 cells were exposed to a series of concentration equal proportion binary mixtures of DES, BPA, DEHP and MEHP with EV for 24, 48, or 72 h, the binary mixtures of EV and the other four EDCs can significantly attenuate cell viability induced by single EV. e antagonistic effects of the binary mixtures of EV and the other four EDCs can be found by detecting cell viability
Single EV, DES, and BPA can promote the proliferation of MCF-7 cells, and EV has the strongest potency in inducing cell proliferation
Summary
Environmental endocrine-disrupting chemicals (EDCs) such as estradiol valerate (EV), diethylstilbestrol (DES), bisphenol A (BPA), diethylhexyl phthalate (DEHP), and mono-2-ethylhexyl phthalate (MEHP) bring up prevalent attention because they have a strong reproductive and developmental toxicity on human and various animal species at low doses [1, 2]. EV is one of the most common sources of free E2 in hormone replacement therapy [3]. EV may act as an endocrine disruptor and adversely affect reproductive outcome [7]. DES was the first synthetic estrogen originally used for clinical therapy to prevent miscarriages. Exposure to DES can cause adverse effects on male and female reproductive tracts in humans, even causing developmental anomalies in subsequent generations [10]
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