Resistance to purine antagonists in experimental leukemia systems.

Resistance to purine analogs by loss of nucleotide-forming capacity was observed in a number of experimental tumor systems. Such resistance frequently was accom panied by loss of specific purine ribonucleotide pyrophosphorylase activities. How ever, it is evident that other mechanisms of resistance to purine analogs also exist both in mouse leukemia and in human leukemia. Attention was focused on a locus of action of 6-mercaptopurine, as the ribonucleo tide, at an early step on the purine biosynthetic pathway—namely, the site of end product inhibition by purine ribonucleotides. In a human neoplasm grown in cell culture, 6-mercaptopurine was a potent inhibitor of this early step in purine biosyn thesis, iii agreement with work in mouse neoplasms.