Abstract in Englisch:

Selenium and copper are essential trace elements with diverse functions for human health. Selenium’s biological functions are mainly attributed to selenoproteins. Copper acts as a structural component, enzymatic cofactor, or metalloallosteric regulator of proteins. Both trace elements are metabolized in the liver, where the selenium-transporting protein SELENOP is synthesized and where copper can interfere with selenium metabolism. In addition, there might be a potential interaction between copper and selenium and dysregulated metabolisms during cancer, since both trace elements seem to accumulate in tumor tissue. Moreover, copper-related proteins and selenoproteins showed a differential expression in tumor cells compared to healthy cells. Several tumor-promoting mechanisms have been described for copper. In contrast, an adequate supply with selenium is supposed to prevent tumor initiation by a concomitant optimized selenoprotein activity. The overall aim of this dissertation was to investigate the interaction between copper and selenium and the role of a modulated supply with copper and selenium in carcinogenesis. This dissertation confirmed an interaction between elevated hepatic copper and selenium metabolism by revealing a copper-induced hepatic SELENOP accumulation and a concomitant decreased systemic selenium status. This might be of special importance for individuals with a prior suboptimal selenium supply and potentially for cancer patients. While results support a tumor-promotive role of copper, physiologically relevant modulated selenium supply was not associated with altered malignant cell transformation. Only supranutritional selenomethionine but not selenite reduced the malignant cell transformation, most probably via mechanisms independent of optimizing selenoprotein synthesis and activity, revealing selenium-species dependent effects. Hence, chemopreventive effects of selenium and the regulation of selenoproteins may be unrelated phenomena.