Response of a Resistant Variant of Leukemic Cells to an Antagonist of Pteroylglutamic Acid

Abstract

The effect of a PGA antagonist, 4-amino-N10 -methyl pteroylglutamic acid on resistant leukemic cells of the mouse has been studied. The development of a florid leukemia with profuse localized growth of lymphomatous tissue, leukocytosis with escape of leukemic cells into the blood and extensive infiltration into various organs occurs at dosage levels as high as the LD50. Symptoms of vit. deficiency did not appear in mice growing the resistant leukemic cells and supplied with a total dose of antagonist as high as 20 mg./kg., indicating that the resistant leukemic cells are metabolizing the antagonist in some manner. Tolerance to 4-amino-N10-methyl-PGA was increased approx. 50-fold. Citrovorum factor did not influence the growth of resistant leukemic cells but partially blocked the optimal growth-promoting effect of the PGA antagonist. Possible mechanisms of action of 4- amino-N10- methyl- PGA on resistant and dependent leukemic cells are considered.