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Comparison of the Effects of 6-Thio- and 6-Methylthiopurine Ribonucleoside Cyclic Monophosphates with Their Corresponding Nucleosides on the Growth of Rat Hepatoma Cells¹

Department of Pharmacology, University of Colorado Medical Center, Denver, Colorado 80262

The cyclic nucleotide forms of 6-mercaptopurine and 6-methylmercaptopurine have been found to be cytotoxic to rat hepatoma cells. Studies with an inhibitor of phosphodiesterase suggest that the cytotoxicity of both cyclic nucleotides results principally from conversion to the 5'-nucleotide. A comparison of the two thiopurine cyclic nucleotides with their nucleoside counterparts has suggested that (a) the thio derivatives act by a common mechanism which is different from that exerted by the methylthio derivatives, and (b) the methylthio cyclic nucleotide acts, at least in part, by a mechanism which differs from that exerted by the methylthio nucleoside.

¹ This work was supported by Grant CA 15687 from the NIH.

Received 4/ 9/76. Accepted 11/24/76.

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