INFLUENCE OF VINBLASTINE ON DNA PARAMETERS AND MULTIDRUG-RESISTANCE IN RENAL-CELL CARCINOMA IN-VITRO

The purpose of this study was to investigate how the vinca alkaloid vi nblastine influences DNA parameters and the mechanisms of multidrug re sistance in renal cell carcinoma. After exposing cell cultures of huma n renal carcinoma to progressively increasing concentrations of vinbla stine the cell lines were examined by flow cytometric DNA analysis to assess the S-phase and G(2)/M-phase fraction and by a modified MTT ass ay. It was shown that the exposed cells became P-glycoprotein-positive by staining the cells with a monoclonal antibody (JSB-1). The flow cy tometric analysis revealed, with prolonged vinblastine exposure, corre lated increases in the S-phase and G(2)/M-phase fractions (P = 0.0001) . When vinblastine-free medium was used for culturing, the changed DNA characteristics returned to their original values. Comparing the DNA parameters with the IC50 (concentration when cell growth is inhibited by 50%) we found a strong correlation between these parameters (P = 0. 0001). In conclusion, DNA analysis of long-term vinblastine exposure m ay provide insight into events leading to multidrug resistance. Furthe rmore, analysis of the DNA profile might also be an important investig ation before planning therapy with vinblastine for renal cell carcinom a.