Copper is an essential dietary micronutrient for a wide range of structural, regulatory, and catalytic functions but even moderately increased concentrations may result in toxicity to cells and tissues. Recent research has greatly enhanced our understanding of metal micronutrients in biological systems, but gaps still exist regarding copper metabolism and regulation and a combination of approaches towards furthering this knowledge are required. To obtain a better understanding of micronutrient interactions within living cells, the research presented in this thesis investigated copper toxicity, resistance and homeostasis by examining the responses of human intestinal Caco-2 cells to exposure of inorganic copper sulfate (CuSO4), organic copper proteinate (Cu Pro) and a chelator used to treat copper overload in Wilson’s disease (triethylenetetramine). The work features: (i) the discovery of non-monotonic dose responses to copper exposure in the Caco-2 cell line; (ii) the establishment of copper tolerant variants in Caco-2 cells and their subsequent characterisation, including proteomic analysis; (iii) microarray profiling of five phenotypically different clones subsequently selected from the copper-resistant Caco-2 variants and investigations of their cross-resistance to other compounds and (iv) proteomic profiling of Caco-2 cells following exposure to triethylenetetramine and subsequent restoration in growth media. These results are detailed in the published research and submitted manuscripts and possible future directions are discussed.