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Synergistic Lethal Effect of cis-Dichlorodiammineplatinum and 1-ß-D-Arabinofuranosylcytosine¹

Clinique des Maladies du Sang, Centre Hospital Universitaire de Strasbourg, 67000 France, and Department of Laboratory Medicine, Physics, and Developmental Therapeutics, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

cis-Dichlorodiammineplatinum(II) and 1-ß-D-arabinofuranosylcytosine display a dramatic synergistic effect when tested in simultaneous combination on LoVo cells, a human colon carcinoma cell line. 1-ß-D-Arabinofuranosylcytosine alone does not induce any cytotoxicity on LoVo cells even at high concentrations but is able to increase up to 1000 times the lethal effects of cis-dichlorodiammineplatinum(II). DNA elution experiments show that 1-ß-D-arabinofuranosylcytosine increases the amount of cis-dichlorodiammineplatinum(II)-induced DNA cross-links. The possible mechanisms of this effect are discussed, and some explanations are proposed.

¹ Supported by Grants CA 23272, CA 17891, and CA 14528 from the National Cancer Institute, Department of Health, Education and Welfare, and Grant CA 16763 through the National Large Bowel Cancer Project.

² To whom requests for reprints should be addressed.

Received 3/10/80. Accepted 9/18/80.

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