Comparison of the effects of 6- thio- and 6-methylthiopurine ribonucleoside cyclic monophosphates withtheir corresponding nucleosides on the growth of rat hepatoma cells.
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.
D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D007289:Cyclic IMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007288:Inosine / Q000031:analogs & derivatives*; D007292:Inosine Nucleotides / Q000031:analogs & derivatives*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008778:Methylthioinosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors; D011684:Purine Nucleosides / Q000494:pharmacology; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D007292:Inosine Nucleotides; D010726:Phosphodiesterase Inhibitors; D011684:Purine Nucleosides; D008778:Methylthioinosine; D007289:Cyclic IMP; D013868:Thioinosine; D007288:Inosine