Quantitative Evaluation of Chemotherapeutic Agents Against Advanced Leukemia in Mice

Abstract

An assay system employing advanced systemic leukemia (L1210) in mice has been utilized to compare the antileukemic effectiveness of a series of chemical agents. Comparison was made of the relative effectiveness of the compounds in increasing the survival time of the mice, employing the folic acid analogue amethopterin as a standard. Data on 38 compounds are presented. Twenty-three of these had been previously studied against early leukemia and in other tumor systems in a comprehensive study of screening (4). None of the compounds used was as effective as amethopterin in increasing the survival time of the leukemic mice. Reserpine, 6-mercaptopurine, thioguanine, 8-azaguanine, and 5-fluorouracil were 50 to 60 percent as effective as amethopterin. Aminopterin, 2 thiadiazole derivatives, azaserine, and 3 pyrimidines showed 30 to 50 percent of the activity of amethopterin. The remaining compounds tested showed lesser or no activity. The application of this type of assay procedure as a tool for screening and the quantitative evaluation of the action of potential antineoplastic agents are discussed.