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The Effect of 8-Azaguanine on Tissue Metabolism in Mice Bearing Sarcoma 37^{* ,}

( Department of Pharmacology, the George Washington University School of Medicine, Washington, D.C.)

1. Data are presented on the effect of 8-azaguanine on the respiration of tissues of CAF₁ mice bearing Sarcoma 37.

2. There was no effect on the respiration of tumor homogenate and tumor, brain, liver, kidney, or spleen slices when the drug was added directly to the respiring tissues. The addition of the supernatant fluid from homogenates of spleen, liver, or kidney incubated with the drug was similarly without effect on the respiration of tumor slices.

3. 8-Azaguanine showed a selective action on tumor tissue after parenteral administration. The minimal effective dose was 200 mg/kg. Two hours after a single dose of 500 mg/kg there was a significant inhibition of respiration, which became almost complete after 24 hours. Forty-eight hours after drug administration, the effect on tumor respiration was diminished.

4. Reversal of 8-azaguanine action was not produced by the administration of guanine.

5. The possible significance of these results has been discussed.

^* This investigation was supported by a research grant from the National Cancer Institute, National Institutes of Health, Public Health Service.

The authors are indebted to Dr. H. George Mandel for the supply of 8-azaguanine and to the National Cancer Institute for the initial tumor and the mice employed in this investigation.

Received 6/30/51.