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Effect of Certain Folic Acid Antagonists on Transplanted Myeloid and Lymphoid Leukemias of the F Strain of Mice^*

Arthur Kirschbaum, Ph.D., M.D., Nancy C. Geisse, M.S., Sister Teresita Judd, Ph.D. and Leo M. Meyer, M.D.

(From the Department of Anatomy, University of Minnesota Medical School, Minneapolis 14, Minn., and Department of Therapeutics, New York University College of Medicine, New York, N.Y.)

Certain folic acid antagonists, including aminopterin and amethopterin, either failed to increase survival time or were less effective than potassium arsenite and ethyl urethan on four transfer lines of myeloid mouse leukemia of the F strain. The chemicals were administered daily in maximum tolerable doses. Treatment was begun 24 hours after transplantation effected by intraperitoneal inoculation of 1,000,000 leukemic cells.

In certain lymphoid transfer lines, amethopterin, a folic acid antagonist, increased survival time to a greater extent than either potassium arsenite or urethan. This inhibiting action was not demonstrable, however, when treatment was begun 8 days after transplantation, untreated controls surviving 10–14 days. Thus, certain agents which increase survival time in specific transplanted leukemias do not affect the course of the disease once the organs are generally infiltrated with leukemic cells. The effectiveness of specific agents is probably due to a delay in the establishment of the usual leukemic cell-host relation of successful transplants.

The inhibiting action of these specific agents on transplanted leukemia has some pharmacologic significance, since even closely related chemicals may be ineffective.

^* This investigation was supported by grants from the American Cancer Society, the National Cancer Institute, and the Cancer Fund of the Graduate School of the University of Minnesota.

Some of the data incorporated within this manuscript have been taken from theses submitted to the Graduate School of the University of Minnesota in partial fulfilment of the requirements for the degree of Master of Science (Nancy C. Geisse) and Doctor of Philosophy (Sister Teresita Judd).

Received 7/16/50.