BINDING OF VINBLASTINE AND ESTRAMUSTINE TO ISOLATED PLASMA-MEMBRANE FRACTIONS FROM HUMAN PROSTATE AND PROSTATIC TUMORS

The binding of vinblastine (VLB) and estramustine (EM) to plasma membr anes isolated from human prostate, prostatic tumors as well as from Du nning rat prostatic AT-I tumors was studied. In addition, the uptake o f these drugs in AT-1 tumor cells in culture was examined. Binding of VLB was six-fold lower than that of EM in membrane preparations from a ll three sources. The uptake of VLB in the intact AT-1 cells was nearl y five-fold lower than that of EM. At concentrations comparable to tho se achieved clinically the binding of EM was 100-fold higher than that of VLB. The data suggest that, owing to a very high membrane concentr ation of EM relative to that of VLB, the active efflux VLB in drug res istant cells would be impeded. This in turn would lead to a higher acc umulation of VLB in cells that actively transport cytotoxic drugs.