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The Effect of cis-Diamminedichloroplatinum(II) on Cultured Human Lymphoma Cells and Its Therapeutic Implications¹

Departments of Clinical Chemistry and Laboratory Medicine [B. D.], Biomathematics [B. W. B.], and Developmental Therapeutics [J. A. G.], M.D. Anderson Hospital and Tumor Institute, Houston, Texas 77025

Asynchronous human lymphoma cells treated for 1 hr with increasing concentrations of cis-diamminedichloroplatinum(II) (DDP) revealed a marked decrease in survival as estimated by the colony-forming technique. When the treatment was extended for 8 hr, a killing effect (more than 3 log decades) was observed for a concentration of 5 µg/ml similar to that obtained with 50 µg/ml incubated with the cells for 1 hr. This finding suggests that better antitumor results with less toxic effects may be obtained clinically by prolonged infusion of low doses of DDP.

Synchronized lymphoma cells showed no significant degree of cell cycle stage sensitivity to DDP. The drug kills cells with similar efficiency in all stages of the cell cycle. No killing effect was elicited after incubation of the cells with spironolactone, a compound said to protect the kidneys from the toxic effect of heavy metals. However, simultaneous incubation of spironolactone and DDP did not prevent the lethal action of the second drug. If spironolactone is proven an inhibitor of DDP nephrotoxicity, it will become a valuable addition to the treatment of human neoplasias with DDP.

¹ Supported by USPHS Grants RR-05511-10 and CA-10379-06. Presented in part at The Second International Symposium on Platinum Coordination Complexes in Cancer Chemotherapy, Oxford, England, April 1973.

Received 6/27/73. Accepted 8/ 6/73.

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