Synergistic toxicity of triethylene thiophosphoramide and folic acid in the IRC-741 leukemia.

The purpose of this study was to determine the influence of folie acid or vitamin B-12 on the course of the IRC 741 rat leukemia treated with thioTEPA. On the first day im mediately following tumor implantation into Fischer rats individual series of these ani mals 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 folie 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, nev ertheless produced remissions consistent with experimental cure. The most important observation, however, was that the concomitant administration of folie acid and a single dose of thioTEPA was associated with premature death of all animals so treated, sug gesting that under certain experimental conditions folie acid may interfere with the ameliorative or curative properties of this particular antileukemic agent. Vitamin B-12 appeared inactive in this experimental system.