Although the toxic effects of cisplatinum on kidney have been appreciated for some time, the renal handling of cisplatinum and the mechanism by which the renal toxicity occurs are still incompletely understood. These mechanisms could be more easily defined if the molecular sites of interaction of cisplatin were recognized. This project is designed to define how the kidney handles cisplatin under normal conditions and after various pretreatments or other experimental conditions. Inherent in this study is an attempt to localize the sites of interaction of cisplatin and its intracellular binding sites. This section reports accumulation rate and decay of Pt-DNA adducts in kidney and gonads, the tissue-specific covalent binding of Pt to renal proteins, and correlations between clinical toxicity observations and renal DNA adduct formation in animals. In addition, data are presented on the pharmacokinetics of dideoxynucleoside antiviral drugs and the metabolic potential of human kidney toward 4- ipomeanol.
