Suppression of phytohemagglutinin-induction of thymidine uptake in guinea pig lymphocytes by methylglyoxal bis(guanylhydrazone) treatment.
Treatment with methylglyoxal bis(guanylhydrazone), a specific inhibitor of S-adenosylmethionine decarboxylase (EC 4.1.1.50), suppressed the phytohemagglutinin-induction of [3H]thymidine uptake by guinea pig lymphocytes. The kinetics of [3H]thymidine uptake revealed that the Km value for thymidine was not changed, but the V value was markedly lowered by the methylglyoxal bis(guanylhydrazone) treatment. The induction of ATP: thymidine 5'-phosphotransferase (EC 2.7.1.75) (thymidine kinase) activity by phytohemagglutinin was suppressed to about the same extent as the induction of thymidine uptake. These suppressions were dependent on the methylglyoxal bis(guanylhydrazone) doses and on duration of the methylglyoxal bis(guanylhydrazone) treatment. Analysis of [3H]thymidine labelled compounds of the acid-soluble fraction showed that conversion of thymidine to thymidine 5'-triphosphate was inhibited by the methylglyoxal bis(guanylhydrazone) treatment. DNA polymerase activity was less inhibited by the methylglyoxal bis(guanylhydrazone) treatment in comparison with the methylglyoxal bis(guanylhydrazone) inhibition of thymidine uptake by whole cells. These results strongly suggested that blocking of polyamine accumulation by the methylglyoxal bis(guanylhydrazone) treatment influenced phytohemagglutinin induction of thymidine phosphorylation, resulting in a decrease of thymidine incorporation into DNA.
D002478:Cells, Cultured; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D007700:Kinetics; D037102:Lectins / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008935:Mitoguazone / Q000494:pharmacology*; D011073:Polyamines / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism*; D013937:Thymidine Kinase / Q000096:biosynthesis; D014529:Uridine / Q000378:metabolism
D006146:Guanidines; D037102:Lectins; D011073:Polyamines; D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase; D007930:Leucine; D008935:Mitoguazone; D013936:Thymidine; D014529:Uridine