Synergistic Effect of 6-Mercaptopurine and 6-Methylmercaptopurine Ribonucleoside on the Levels of Adenine Nucleotides of Sarcoma 180 Cells

Summary The synergistic antitumor action of 6-mercaptopurine (6-MP) and 6-methylmercaptopurine ribonucleoside (MMPR) is confirmed with Sarcoma 180 ascites cells. Striking decreases are seen in the adenine nucleotide concentrations in cells incubated for 1 hr with this drug combination, and lesser effects are seen on the guanine nucleotide concentrations. Still greater decreases in adenine nucleotide levels are observed when the cells are preincubated for 30 min with MMPR before addition of 6-MP. The 5′-monophosphate nucleotides of 6-MP and MMPR were synthesized in Sarcoma 180 cells without mutual interference and, in addition, stimulation of 6-thioinosine 5′-phosphate formation occurred when the cells were preincubated with MMPR. The formation of MMPR-5′-P from 6-MP shown in other tumors was demonstrated in Sarcoma 180 cells. It was also shown that this conversion was inhibited in cells incubated with MMPR, suggesting a product inhibition of the enzyme system responsible for this S -methylation.