The role of methylmercury on thioredoxin reductase activity in breast cancer cells.
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Metalloestrogens are small ionic metals and metalloids that activate the estrogen receptor (ER) in a manner similar to estrogen. When metalloestrogens bind to the ER, there is an increase in the expression of estrogen-related genes and proliferation of estrogen-dependent breast cancer. Mercury has been shown to cause proliferation of estrogen-dependent breast cancer cells through its role as a metalloestrogen. Mercury, in the form of methylmercury (MeHg), induces oxidative stress via overproduction of reactive oxygen species (ROS), and inhibits cellular antioxidant defense mechanisms. Specifically, MeHg inhibits the enzyme thioredoxin reductase (TrxR), which is a crucial enzyme involved in the scavenging of ROS and plays a role in many signaling pathways. In this study, a method for measuring TrxR activity in cell culture and tissues was developed. Furthermore, a method for measuring ROS levels in zebrafish tissue was perfected and used to determine ROS concentration in the tissues of tumor and non-tumor bearing fish. Although the method for measuring TrxR activity in cells and tissue remains to be perfected, ROS levels measured in the gastrointestinal (GI) system of tumor-bearing fish were significantly greater than those in nontumor bearing (control) fish. This result was consistent with the observation of tumor formation in the GI system. Further studies using methylmercury must be performed in order to decipher its role in tumor formation and ROS production in vivo.
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Brandon Conn's Honors Thesis .pdf