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Synergistic Toxicity of Triethylene Thiophosphoramide and Folic Acid in the IRC 741 Leukemia^*

Doris McKenzie and Jerome I. Brody

( Department of Medicine, Veterans Administration Hospital, and the University of Miami School of Medicine, Coral Gables, Florida)

The purpose of this study was to determine the influence of folic acid or vitamin B-12 on the course of the IRC 741 rat leukemia treated with thioTEPA. On the first day immediately following tumor implantation into Fischer rats individual series of these animals were given 6 mg/kg thioTEPA, in a single injection, or 1 mg/kg, every other day for six doses without and with simultaneous injections of folic acid or vitamin B-12. ThioTEPA alone, in multiple doses, increased the rat survival time, but these animals eventually died of leukemia. ThioTEPA in a single injection, although more toxic, nevertheless produced remissions consistent with experimental cure. The most important observation, however, was that the concomitant administration of folic acid and a single dose of thioTEPA was associated with premature death of all animals so treated, suggesting that under certain experimental conditions folic acid may interfere with the ameliorative or curative properties of this particular antileukemic agent. Vitamin B-12 appeared inactive in this experimental system.

^* Presented in part to the National Meeting of the American Association for Cancer Research, Atlantic City, New Jersey, April 15, 1962.

United States Public Health Service Research Fellow in Hematology. Present Address: Jackson Memorial Hospital, Miami, Florida.

Present address: The Graduate Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Received 7/ 9/62.