Comparison of specificity of inhibition of polyamine synthesis in bovine lymphocytes by ethylglyoxal bis(guanylhydrazone) and methylglyoxal bis(guanylhydrazone).
Ethylglyoxal bis(guanylhydrazone) (EGBG) was compared as an inhibitor of polyamine biosynthesis with methylglyoxal bis(guanylhydrazone) (MGBG) in bovine small lymphocytes stimulated by concanavalin A. EGBG brought about a decrease in spermidine and spermine levels equal to that found with MGBG, but at a 5-fold lower intracellular drug concentration. Despite identical polyamine levels, the degree of inhibition of DNA and protein synthesis by EGBG was smaller than that observed with MGBG, in either the presence or absence of the ornithine decarboxylase inhibitor, alpha-difluoromethylornithine. It was found that in vitro protein synthesis and in vivo mitochondrial function were inhibited by concentrations of MGBG necessary to inhibit polyamine synthesis in cells (1 to 3 mM), but not by efficacious levels of EGBG (0.2 to 0.6 mM). These results suggest that EGBG is more suitable as a specific inhibitor of polyamine biosynthesis and that use of this drug, rather than MGBG, in combination with alpha-difluoromethylornithine may be useful for studying the physiological functions of polyamines in animal cells.
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003208:Concanavalin A; D004261:DNA Replication / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008935:Mitoguazone / Q000031:analogs & derivatives / Q000494:pharmacology*; D011073:Polyamines / Q000096:biosynthesis*; D014176:Protein Biosynthesis / Q000187:drug effects; D013329:Structure-Activity Relationship
D006146:Guanidines; D011073:Polyamines; D003208:Concanavalin A; C041127:ethylglyoxal bis(guanylhydrazone); D008935:Mitoguazone