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The Effect of 5-Amino-7-Hydroxy-1H-v-Triazolo (d) Pyrimidine (Guanazolo) on a Variety of Neoplasms in Experimental Animals^*

Alfred Gellhorn, M.D., Morris Engelman, Ph.D., Daniel Shapiro, M.D., Samuel Graff, Ph.D. and Horace Gillespie, Ph.D.

(From the Institute of Cancer Research and the Departments of Medicine, Surgery, Biochemistry, and Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York)

The action of the guanine analog, 5-amino-7-hydroxy-1H-v-triazolo (d) pyrimidine, on a variety of experimental tumors has been reported. Three transplantable adenocarcinomas of the breast in mice (755, RC, and Eo771) were effectively inhibited by the chemical agent, whether therapy was instituted shortly after transplantation or after the tumor had become well established; anterior chamber transplants of an undifferentiated squamous-cell carcinoma (Brown-Pearce) in rabbits' eyes were similarly controlled by the triazolopyrimidine. No demonstrable inhibitory effects of the chemical on an undifferentiated sarcoma (Sarcoma 180) could be detected, nor was there any apparent inhibition of an acute leukemia (9417) or lymphosarcoma (6C3HED) in preliminary experiments, with the dosage employed.

Using the changes in body weight during therapy as an over-all index of toxicity of the triazolopyrimidine, it was observed that the therapeutic activity of the drug against the tumors was not associated with significant toxicity to the host.

In spite of convincing evidence of tumor inhibition, no regression of established neoplasms under therapy was observed, and the viability of inhibited cells was unimpaired, as indicated by their ability to reproduce normally on subsequent transplantation. With the exception of the Brown-Pearce carcinoma, no morphological changes in the tumors of treated animals could be detected.

The results presented in this report fail to confirm the hypothesis of a uniform chemical pattern in all neoplastic tissue. However, the evidence at hand suggests that the triazolopyrimidine distinguishes a biochemical difference between normal tissues and certain carcinomas.

^* This work was supported by grants from the American Cancer Society on the recommendation of the Committee on Growth of the National Research Council.

Damon Runyon Clinical Research Fellow.

Received 11/26/49.