Polyamines antagonize both the antileukemic activity and the reverse transcriptase stimulatory activity of 4,4'-diacetyldiphenylurea bis(guanylhydrazone) (DDUG).
(Diacetyldiphenylurea)bis(guanylhydrazone) (DDUG) functions as a cationic trypanocide antagonized in vivo by exogenous concomitant addition of the biologically active polyamine, spermine. It also inhibits the DNA polymerases of L1210 murine leukemia cells. We have found that DDUG stimulates Rauscher murine leukemia virus DNA polymerase activity in a manner similar to polyamines. Such stimulation does not occur if DNA synthesis is carried out on spermine + activated DNA complexes. We also show that the in vivo antileukemic activity of DDUG in the L1210 ascites mouse model is antagonized by biologically active polyamines. These studies suggest a new intracellular target for the antileukemic activity of DDUG: interference with polyamine function.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002224:Carbanilides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004279:DNA, Viral / Q000096:biosynthesis; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011073:Polyamines / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000032:analysis*; D011925:Rauscher Virus / Q000201:enzymology
D000970:Antineoplastic Agents; D002224:Carbanilides; D004279:DNA, Viral; D011073:Polyamines; C100261:diacetyldiphenylurea bisguanylhydrazone; D012194:RNA-Directed DNA Polymerase