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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Inhibition of human lymphoma DNA-dependent RNA polymerase activity by 6-mercaptopurine ribonucleoside triphosphate.

6-Mercaptopurine was found to inhibit the growth of cultured human lymphoma P3HR-1 cells and the incorporation of [3H]-uridine into trichloroacetic acid-precipitable materials of the cells. One of the derivatives of 6-mercaptopurine, 6-mercaptopurine ribonucleoside triphosphate (6-thio-ITP), was found to inhibit in vitro RNA synthesis (both engaged and free enzyme activities) of the isolated nuclei from P3HR-1 cells. The alpha-amanitin-resistant RNA polymerase (polymerase I) and alpha-amanitin-sensitive RNA polymerase (polymerase II) of the cells were isolated and partially purified by either diethylaminoethyl cellulose or diethylaminoethyl Sephadex column chromatography, followed by DNA-cellulose affinity chromatography. It was found that these partially purified enzymes were also sensitive to 6-thio-ITP inhibition. Kinetic studies showed that the inhibition of RNA polymerase activities by 6-thio-ITP could be reversed by increasing concentrations of guanosine 5'-triphosphate in the reaction mixture, indicating that 6-thio-ITP may act as a competitive inhibitor of the enzymes by competing with guanosine 5'-triphosphate for its enzyme-binding site. These data suggest that inhibition of RNA transcription by 6-thio-ITP may be considered as one of the mechanisms of the cytotoxic action of 6-mercaptopurine in human tumor cells.[1]

References

  1. Inhibition of human lymphoma DNA-dependent RNA polymerase activity by 6-mercaptopurine ribonucleoside triphosphate. Kawahata, R.T., Chuang, L.F., Holmberg, C.A., Osburn, B.I., Chuang, R.Y. Cancer Res. (1983) [Pubmed]
 
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