Molecular Pharmacology, Vol 18, 503-506, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Effect of 6-Mercaptopurine Ribonucleotides on DNA-Dependent RNA Polymerase Activity

¹ Departments of Pharmacology and Veterinary Pathology, University of California, Davis, California 95616, Department of Veterinary Pathology, Texas A & M University, College Station, Texas 77843, and Department of Biochemistry, Oral Roberts University, Tulsa, Oklahoma 74171

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.