596 THE BIOCHEMISTRY OF B VITAMINS 



protect approximately 60, 50 and 10 per cent of baby chicks against the 

 toxic effect of 10 y doses of 4-amino-4-desoxyfolic acid which are other- 

 wise fatal. The antagonist under these conditions did not prevent tumor 

 growth in baby chicks. 



Leukemia. The greater sensitivity to folic acid deficiency of leuco- 

 poiesis in the myeloid series 107 led to the suggestion that folic acid 

 analogues might be used as chemotherapeutic agents in myelogenous 

 leukemia. 



In a preliminary report on the use of folic acid derivatives in the 

 treatment of human leukemia m it is indicated that pteroyldi-y-glutamyl- 

 glutamic acid, pteroyldiglutamic acid, pteroylaspartic acid and N-methyl- 

 pteroic acid do not alter the blood picture or bone marrow in cases of 

 chronic leukemia and multiple myeloma; however, in cases of acute 

 leukemia, administration of the folic acid antagonists resulted in a tem- 

 porary reduction of the total white cells. 173 



A preliminary report of the effect of inhibitory folic acid analogues on 

 acute leukemia in children indicated that temporary remissions can be 

 induced with 4-amino-4-desoxyfolic acid. 174 The effect of N 10 -methyl- 

 pteroic acid and pteroylaspartic acid is questionable. Upon treatment with 

 4-amino-4-desoxyfolic acid, the white cell count tended to return to a 

 normal level both in patients with an initially high count and in those 

 with marked leukopenia at the outset of the therapy. A decline was 

 observed in the percentage of immature cells with a marked decrease in 

 blast forms, which disappeared in some cases from the peripheral blood. 

 The relative percentages of mature leucocytes approached normal values 

 in the peripheral blood. In the bone marrow a decrease or disappearance 

 of leukemic cells and variation from hypoplasia to almost normal pattern 

 was observed. However, the analogue is toxic, giving effects which include 

 stomatitis with early ulceration. Indications are that the remissions are 

 only temporary. Similar temporary favorable results have been reported 

 by others. 175 



Only slight and irregular effects in increasing the survival time of mice 

 injected with transmitted leukemia Ak 1394 and Akm 9417 are obtained 

 on administration of 4-amino-4-desoxyfolic acid which was, however, 

 somewhat more effective against the Ak 4 and C 1498 strains of leu- 

 kemia. 176 4-Amino-N 10 -methyl-4-desoxyfolic acid allowed a longer sur- 

 vival time than did nitrogen mustards in mice injected with Akm 9417, 

 Ak 4 or C 1498 strains of leukemia, but was not effective with the Ak 1394 

 strain. Nitrogen mustards allow a slight increase in survival time of mice 

 with the C 1498 strain, but 4-amino-N 10 -methyl-4-desoxyfolic acid in- 

 creases the survival time slightly more than 200 per cent. By the cytocidal 

 method, no activity could be shown against the cells of leukemia Akm 



