Molecular Mechanisms of Estrogenic Xenobiotica
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Abstract
In this thesis I investigate the effect of ten compounds associated with microplastic on the human estrogen receptor α. Microplastics contain plasticizers such as bisphenols, phthalates and organophosphate esters, among others. In addition, hydrophobic chemicals can accumulate on the plastic, such as polycyclic aromatic hydrocarbons. After ingestion of the microplastic by marine animals, these substances can dissolve out of the microplastic and thus also enter human food.
Through molecular docking simulations, in vitro experiments in cell cultures, and next generation sequencing, I can show that bisphenol A, bisphenol B, bisphenol Z, tetramethyl bisphenol A, benzyl butyl phthalate, butyl cyclohexyl phthalate, butyl octyl phthalate, tri-o-cresyl phosphate, indeno[1,2,3-cd]pyrene, and picene can bind to the estrogen receptor α in silico and in vitro. In addition, BPA, tetramethyl bisphenol A, and the three phathalates were able to activate the receptor. A proliferative effect was observed with bisphenol B and tetramethyl bisphenol A. In addition, all investigated substances affected gene expression in MCF-7 cells favoring tumorigenesis. All substances are to be considered potentially harmful to health due to their interaction with the human estrogen receptor α.