The mechanisms by which carcinogenic chemicals and oncogenic viruses can transform proximal tubule cells of the kidney are largely unknown. Since the proximal tubule epithelial cells are the progenitors of most renal neoplasms, it is important to define their growth and differentiation programs in order to understand renal cancer. We will design a model to study renal carcinogenesis using pure rat kidney proximal tubule cells (RPTE) in culture. RPTE will be established in culture using selective techniques to insure a pure population. Cells will be transformed in vitro by known renal carcinogens and DNA-tumor viruses. Selection techniques for isolating transformed cells will be used both to quantitate the frequency of transformation and to prepare cells for further studies on the mechanism of transformation. The model will be used to determine the transformation potential of a novel group of toxins, S-cysteine conjugates, which may be the carcinogenic species produced from some xenobiotics. The growth factor requirements of transformed cells will be determined. These studies will provide a much needed data base for the investigation of renal carcinogenesis and the transformation of proximal tubule epithelial cells. In the future, the model will be extended into human studies.
