Prevention of Chemotherapeutic Effects of 4-Amino-N10-Methyl-Pteroylglutamic Acid on Mouse Leukemia by Pteroylglutamic Acid.

Abstract

In an attempt to elucidate the mode of action of the 4-amino antagonists of pteroylglutamic acid (PGA) against leukemia cells, an investigation was undertaken to determine whether prior administration of PGA could prevent the chemotherapeutic effect of 4-amino-N10-methyl-PGA. Transmitted leukemia Ak 4 was used and results were based on survival time. PGA was injd. at the rate of 60, 30, 15, and 3 mg. kg., while the 4-amino-N10 methyl-PGA was injd. 1 hr. later at 3 mg./kg. Mice treated with the antagonist alone survived at least twice as long as the controls, while those given PGA at 30-60 mg./kg. prior to the antagonist died at approx. the same time as the controls. Similar results were achieved with pteroyltriglutamic acid (PTGA) at 50-400 mg./kg. These studies indicate that the chemotherapeutic effect of 4-amino-N10 methyl-PGA can be prevented by prior administration of 10-20 times as much PGA or 17-125 times as much PTGA.