Effect of 6-mercaptopurine ribonucleotides on DNA-dependent RNA polymerase activity

6-Mercaptopurine ribonucleoside 5'-triphosphate was found to be an inhibitor of DNA-dependent RNA polymerases from Escherichia coli and chicken myeloblastosis cells. The inhibitor appears to compete with GTP for its binding to RNA polymerase, resulting in a reduction of RNA chain initiations. Neither 6-mercaptopurine ribonucleoside nor its monophosphate derivative caused the inhibition. These studies suggest that the antineoplastic action of 6-mercaptopurine may in part be owing to the inhibition of the activity of DNA-dependent RNA polymerase, resulting in an inhibition of cellular RNA synthesis.