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A Model System for Detecting Drug Impairment of Antitumor Host Defenses¹

Departments of Experimental Therapeutics and Biostatistics, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14203

A model system was developed taking advantage of the fact that the complete regression of Sarcoma 180 in vitamin B₆-deficient Swiss mice is due to the immunological response of the host directed against the tumor. By comparing the effects of drug treatments given before or after tumor implantation, it was possible to dissociate the antitumor from the antihost effects of the drugs tested. The model uses four response indices: (a) initial tumor growth inhibition, (b) tumor regression during the second week following implantation, (c) mortality in relation to time of death and size of tumors prior to death, and (d) incidence of complete tumor regression. Of the 27 drugs tested, 6-mercaptopurine and kethoxal-bis(thiosemicarbazone) inhibited only the growth of the tumor. Both the immunological response of the host directed against the tumor and the growth of the tumor were inhibited by arabinosylcytosine, cyclophosphamide, and nine other compounds. The host response to the tumor was inhibited by 4-deoxypyridoxine, nitrogen mustard, and ten other agents without significant effect on tumor growth.

¹ This investigation was supported in part by Research Grants CA-04130 and CA-11047 from the National Cancer Institute, USPHS.

Received 5/ 5/69. Accepted 12/19/69.