Date of Graduation


Document Type


Degree Type



School of Medicine


Physiology, Pharmacology & Neuroscience

Committee Chair

Joginder Nath.


The third isoform of metallothionein, MT-3 is shown to have a restricted pattern of tissue distribution with expression confined to the neural tissue. Previous work done by this laboratory has shown that MT-3 is not expressed in the normal bladder but is over-expressed in bladder cancer with levels correlating to the type and grade of tumor. Recently, a new bladder epithelial cell line UROtsa has been characterized that does not express the MT-3 gene and may serve as a useful in vitro model system of the normal human urothelium. The goal of this study was to see the effect of MT-3 over expression in the normal human bladder epithelial cell line. The MT-3 transfected cells expressed the mRNA for the MT-3 gene but expressed very little MT-3 protein. Treatment with cadmium or zinc did not increase the level of MT-3 protein in MT-3 transfected clones. Otherwise MT-1E transfected UROtsa cells showed increased both mRNA and protein by exposure to cadmium. These data suggests that the MT-1/2 and MT-3 are regulated different ways. In vitro transformation model systems are very useful tools in the understanding of fundamental differences between normal cells and tumor cells if both have been derived from a common source. We showed the malignant transformation of normal human urothelial cell line by chronic exposure to cadmium or arsenic in vitro. The malignant transformation of these exposed cells was confirmed by increased growth rate, anchorage independent growth, and tumor development in nude mouse. The malignant transformation of normal human urothelial cells is compelling evidence that arsenic and cadmium have the potential to be human bladder.