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Time- and Concentration-dependent Inhibition of the Clonogenic Growth of N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide-induced Murine Bladder Tumor Cell Lines by cis-Diamminedichloroplatinum(II)¹

Departments of Internal Medicine [H. B. N.], Pharmacy Practice [C. A. W.], and Urology [D. D. M., M. S. S.], University of Tennessee Center for the Health Sciences, Memphis, Tennessee 38163

The influence of the concentration and time of exposure to cis-diamminedichloroplatinum on the inhibition of the clonogenic growth of three N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide mouse bladder tumor cell lines was evaluated in a tumor colony assay. Drug testing was performed in the murine model, and tumor cells were removed from the animals for in vitro testing. Murine drug testing revealed marked cis-diamminedichloroplatinum sensitivity of all three mouse bladder tumor lines. One-hr incubation in cis-diamminedichloroplatinum was an inadequate time of drug exposure to produce in vitro colony survival curves predictive of in vivo sensitivity to the drug. Furthermore, it was found that 6- to greater than 24-hr exposure to the drug was required to produce colony survival curves in the tumor colony assay predictive of tumor sensitivity. High drug concentrations using 1-hr drug incubation or continuous incubation in drug both produced colony survival curves predictive of tumor sensitivity. Both methods, however, would require higher products of the drug concentration multiplied by time curves than could theoretically be clinically achievable in the murine model. Until pharmacokinetic data on cis-diamminedichloroplatinum are available in this murine model, higher drug sensitivity boundaries than are presently being used for other chemotherapeutic agents will have to be utilized when testing these mouse bladder tumor cell lines for their sensitivity to cis-diamminedichloroplatinum in a tumor colony assay.

¹ This research was supported by American Cancer Society Grants IN-85-N9 and IN-85-N7.

² To whom requests for reprints should be addressed, at Hematology/Oncology Section, Coleman Research Building, 956 Court Street, Memphis, Tenn. 38163.

Received 2/ 3/81. Accepted 11/30/81.