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6-Mercaptopurine: Effects in Mouse Sarcoma 180 and in Normal Animals^*

( Division of Experimental Chemotheraphy, Sloan-Kettering Institute, New York, N.Y., and Wellcomse Research Laboratories, Tuckahoe, N.Y.)

6-Mercaptopurine, a purine antagonist for L. casei, has been shown to possess unique activity as an inhibitor of the experimental mouse tumor, S-180. The compound prolongs survival time of mice bearing this tumor and, in fact, induces complete recovery in a significant number of animals. These effects may be seen when treatment is initiated either 24 or 96 hours after implantation and when the agent is given by the oral or intraperitoneal route. Cytological disturbance is induced in the tumor to an extent such that the majority of cells lose their characteristic viability when transplanted to normal mice. Finally, a tumor has been developed which demonstrates resistance to 6-mercaptopurine; the implications inherent in this observation may represent a guide in the clinical applications of the agent.

The toxicity of 6-mercaptopurine has been studied in mice, rats, cats, and dogs. No acute deaths were seen. In general, disturbances induced by this agent were referable to the hematopoietic system, the gastrointestinal tract, and the liver. Rats, when exposed to the compound, differed from the other species studied in that myocarditis and pulmonary lesions with effusion developed. 6-Mercaptopurine has been advanced to the stage of clinical evaluation with interesting results.

^* This investigation was supported by an institutional grant from the American Cancer Society and by grant C-415 from the National Cancer Institute of the National Institutes of Health, U.S. Public Health Service, to Sloan-Kettering Institute, and assisted by a grant from the Charles F. Kettering Foundation to the Wellcome Research Laboratories.

Received 3/30/53.

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