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Inhibition of Ascites Cell Growth by Combinations of 6-Thioguanine and Azaserine^*

Alan C. Sartorelli and G. A. LePage

( McArdle Memorial Laboratory, Medical School, University of Wisconsin, Madison 6, Wis.)

The Ehrlich ascites carcinoma, the Sarcoma 180 ascites, and the TA 3 ascites carcinoma were found to be sensitive to combinations of azaserine plus thioguanine. The Mecca lymphosarcoma in either solid or ascites form and the 6C3HED lymphosarcoma ascites proved to be relatively resistant. The most effective dose schedule tried was 0.2 mg/kg azaserine plus 0.5 mg/kg thioguanine, given twice daily, beginning 1 day after the tumors were transplanted. After 6 days of this therapy, 50 per cent of mice transplanted with Ehrlich ascites carcinoma, 60 per cent of mice transplanted with Sarcoma 180 ascites, and 23 per cent of mice transplanted with TA3 ascites carcinoma were found to be tumor-free.

Simultaneous therapy of 0.2 mg/kg of azaserine plus 0.5 mg/kg of thioguanine, both injected at approximately 8:00 A.M. daily for 6 days, was much more effective than alternate therapy, which consisted of 0.2 mg/kg of azaserine at approximately 8:00 A.M. and 0.5 mg/kg of thioguanine at Approximately 8:00 P.M. for a total of 6 days. This indicates that, for maximum tumor inhibition, thioguanine and azaserine must be administered simultaneously, supporting the concept that the two drugs establish concurrent blocks of purine nucleotide synthesis.

^* This research was supported in part by United States Public Health Service, Grant No. C2491, and in part by the Alexander and Margaret Stewart Fund.

Present address: The Samuel Roberts Noble Foundation, Inc., Biomedical Division, Ardmore, Oklahoma.

Received 3/31/58.