Synergistic inhibitory action of a-methopterin and a diaminopyrimidine upon leukemia L1210 in mice.

INTRODUCTION Certain 2,4-diaminopyrimidines, synthesized for possible use as metabolic antagonists, were found to have antimalarial activity (3, 5). These pyrimidines were also able to inhibit the growth of L. casei and L. citrovorum, and this effect could be reversed by folie acid or by folinic acid (4-8). For this reason it has been proposed that these pyrimi dines probably inhibited the folie acid-folinic acid conversion (1, 3, 5), as has been proposed for the folie acid analogs (14, 19). This hypothesis has re ceived support from the reports that Sarcoma 180 (2) and leukemia Ak4 (1), tumors inhibited by folie acid analogs, were also inhibited by these pyrimidines. Data are herewith presented on the effect of one of these drugs, 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (W-50-197)1 on the survival time and tumor size in mice inoculated with the transplantable leukemia L1210 (11). These effects are compared to the effects of Amethopterin when given alone and to the effects when the two drugs are given in combination.