Effects Of Typical Environmental Endocrine Disrupting Chemicals On MCF-7Cell Proliferation And Analysis Of The Mechanism

Estrogen compounds as the typical environmental endocrine disrupting chemicals(EDCs) have a strong reproductive and developmental toxicity at low doses, which isbecoming one of the hot spots of research in the environmental toxicology field.Estradiol (E2), estradiol valerate (EV), diethylstilbestrol (DES), bisphenol A (BPA),di(2-ethyl hexyl) phthalate ester(DEHP) and its metabolite MEHP are considered asthe typical estrogen compounds and widely exist in the aquatic environment, causingpeople’s attention, therefore their joint toxicity effects and mechanism need furtherstudy strengthly.This paper tested the single toxicity of the typical estrogen compounds on MCF-7cell as well as their joint toxicity under the different experimental designs using thehuman breast cancer cell MCF-7proliferation assay. At the same time, weinvestigated the proliferation toxicity mechanism of the target compounds to MCF-7cells from the the expression of estrogen receptor ERα protin and the change ofintracellular ROS levels. Finally, we studied the composite toxicity effect of thesediment organic extracts on the proliferation toxicity of MCF-7cells from theHuangpu River and Suzhou Creek, as well as the effect on ROS levels in the cell. Themain results are as follows:(1) E2, EV, DES, BPA promoted the proliferation of MCF-7human breast cancercells, while DEHP, MEHP had no effect on proliferation of MCF-7cells; In the twoexperimental designs of factorial experiment and equal concentration ratio, weconcluded that the binary mixture with DES and EV was an additive effect or close tothe additive effect on the proliferation of MCF-7cells.(2) Target compounds E2, DES, BPA promoted the MCF-7cell proliferationmainly by the estrogen receptor (ER) pathway because of a clear expression of ERreceptor protein in MCF-7cells. In addition, E2, EV and BPA can regulate the ROSlevels in MCF-7cells. They induced oxidative stress and maintained intracellularredox homeostasis through their oxidation resistance mechanisms. The impact of DES and DEHP on ROS level in the cell was not obvious; The ROS level had not changedby the bindary mixtures of DES, BPA with EV, compared with their single role onROS level.(3) The toxicity test results of sediment organic extracts from the Huangpu Riverand Suzhou Creek on the proliferation of MCF-7cells showed that most of thesamples had different degree toxic effects on MCF-7cell proliferation and presenteddose-effect dependent and time-effect dependent relationships. They also had a certainimpact on ROS level in the MCF-7cells. We can conclude that Huangpu River andSuzhou Creek sediments were polluted by some organic toxicity pollutants, butfurther chemical analysis was needed to confirm the types of organic pollutants.