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Further Evidence on the Mode of Action of 8-Azaguanine (Guanazolo) in Tumor Inhibition^*

(From the Biological Laboratory, Amherst College, and the Zoölogical Laboratory, University of Massachusetts, Amherst, Mass.)

1. The guanine analog, 8-azaguanine (guanazolo) has been found carcinostatic for adenocarcinoma 755 and Lymphoma 2, thus confirming earlier observations (4, 9, 10).

2. Leukemia P1534 in dba mice and spontaneous adenocarcinoma of Swiss mice were also inhibited by the administration of 8-azaguanine.

3. Sarcoma 37 in C57 black mice and melanoma S 91 in dba mice were not inhibited by the administration of 8-azaguanine.

4. The ineffectiveness of 8-azaguanine in the inhibition of Sarcoma 180 and Lymphosarcoma 6C3HED was confirmed (4, 17, 18).

5. Dose-response tests with 8-azaguanine on tumor 755 and Lymphoma 2 show that these tumors respond in a regular manner to increasing concentrations of the compound.

6. Definite, though incomplete, reversal of the inhibition of the growth of tumor 755 produced by 8-azaguanine was obtained with guanine.

7. It was shown that tumor 755 and Lymphoma 2 are inhibited by 8-azaguanine even after the implants have been established for relatively long periods of time.

8. The adenine analog, 8-azadenine, was found to be relatively inactive as an inhibitor for tumor 755, while 2-mercapto-8-azadenine was inert.

9. The available evidence is discussed for its bearing on the question of the existence of a fundamental biochemical difference between certain tumor cells and normal mammalian cells.

^* Supported by a grant from Research Corporation and a grant from the American Cancer Society on recommendation by the Committee on Growth.

Received 11/ 8/50.