Response of murine erythroleukemia cells to cis- and trans-diamminedichloroplatinum (II)

Cis-diamminedichloroplatinum II (cis-DDP), an antitumor drug and the inactive trans-isomer were studied to evaluate their effects on cell multiplication, DNA synthesis, and surface morphology of the murine erythroleukemia cells (clone 6A11A). Short-term treatment of cells (1 h) with 5 and 10 micrograms/ml of cis-DDP resulted in a significant inhibition of cell multiplication. Continuous treatment with cis-DDP (up to 144 h) significantly arrested cell growth at 1, 5, and 10 micrograms/ml. The cells exposed to 10 micrograms/ml trans-DDP exhibited a slight decrease in cell multiplication; however, the 25-micrograms/ml treatments showed a modest inhibition of cell growth. Continuous treatment with cis-DDP resulted in a concentration-dependent decrease in DNA synthesis, although low-dose treatment (0.05 and 0.1 microgram/ml), with a few exceptions, had no relative inhibitory effect. Likewise, trans-DDP treatments decreased tritiated thymidine incorporation; however, this inhibitory effect was not as drastic as with corresponding concentrations of cis-DDP. Scanning electron microscope studies revealed the formation of many giant cells and blebs at all short-term treatment concentrations of cis-DDP past the 48 h interval. Continuous treatment of cis-DDP at 1 micrograms/ml concentration produced giant cells with minute holes, whereas the 5 and 10 micrograms/ml exposure resulted in the formation of blebs and large holes and reduction of microvilli past the 48-h treatment period. At higher concentrations the continuous treatment of cis-DDP completely destroyed the cells. The surface morphology of trans-isomer treated cells, in most instances, resembled the corresponding untreated control cells.