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Effect of Selenium in Combination with cis-Diamminedichloroplatinum(II) in the Treatment of Murine Fibrosarcoma

SC 27 Inserm, Laboratoire de Biophysique, Faculté de Médecine, 94010 Creteil [J-P. B.], and Institut de Recherches Scientifiques sur le Cancer, 94802 Villejuif [C. P., S. T., G. L.], France

cis-Diamminedichloroplatinum(II) (cis-DDP) is a well-known anticancer agent the use of which is limited by its toxicity. Since it has been demonstrated that selenium is able to combine with metals like cadmium and mercury and to reduce their toxicity, we decided to investigate whether it could reduce the toxicity of platinum. We treated fibrosarcoma-bearing mice with a combination of cis-DDP and selenium. The dose of 2 or 4 µg selenium/g animal weight had no effect on tumor growth. The i.p. injection of 16 µg cis-DDP/g led to early death of animals. The i.p. treatment of tumor-bearing animals with 2 or 4 µg of selenium reduced the early mortality induced by cis-DDP at a dose of 16 µg/g. Therefore, the addition of selenium allowed the administration of high doses of cis-DDP, which resulted in an improved antitumor effect.

Clonogenic assays following drug exposure showed that selenium had no direct effect on tumor cells and did not modify the antitumor activity of cis-DDP. Electron microscopy showed reduced changes in renal cells when selenium was added to the cis-DDP treatment. Microanalysis showed no accumulation of either selenium or platinum within renal cells.

These results suggest that the addition of selenium decreases the nephrotoxicity of cis-DDP.

¹ To whom requests for reprints should be addressed.

Received 8/ 9/83. Accepted 4/ 3/84.