MODULATION BY CIS-DIAMMINEDICHLOROPLATINUM (II) OF THE SUSCEPTIBILITIES OF HUMAN T24 LINED AND FRESHLY SEPARATED AUTOLOGOUS URINARY-BLADDER TRANSITIONAL CARCINOMA-CELLS TO PERIPHERAL-BLOOD LYMPHOCYTES AND LYMPHOKINE ACTIVATED KILLER-CELLS

The effects of cis-diamminedichloroplatinum (II) on the susceptibilities of human T24 lined and freshly separated autologous urinary bladder transitional carcinoma cells to lysis by peripheral blood lymphocytes of patients with urinary bladder cancer was analysed in a 12-hour Cr-51 release assay. Treatment of T24 cells with cis-diamminedichloroplatinum (II) at 10-mu-g./ml. for three hours enhanced their susceptibility to peripheral blood lymphocytes and lymphokine activated killer cells. Kinetics studies demonstrated that the enhancement of their susceptibility became noticeable by three hours and continued until 12 hours. The susceptibilities of autologous tumor cells to both large granular lymphocytes and T lymphocytes were also enhanced by treatment of them with cis-diamminedichloroplatinum (II). There was no significant difference in the number of peripheral blood lymphocytes binding to cis-diamminedichloroplatinum (II)-treated T24 cells as compared with untreated T24 cells. Treatment of T24 cells with mitomycin C did not change their natural killer sensitivity. Pretreatment of T24 cells with cis-diamminedichloroplatinum (II) and lysosomotrophic agents (L-leucin-methyl-ester or chloroquine) reduced the enhancement of their susceptibility to natural killer cells by cis-diamminedichloroplatinum (II) alone. On the other hand, pretreatment of peripheral blood lymphocytes with cis-diamminedichloroplatinum (II) had no influence on the cytotoxicity against T24 cells. These results indicate that cis-diamminedichloroplatinum (II) may have an augmenting effect on the susceptibility of tumor cells to the cell-mediated cytotoxicity partly through a modification of cell membrane independently of its antimetabolic activity and this modification may be one of the possible mechanisms responsible for tumor regression after chemotherapy with cis-diamminedichloroplatinum (II).