Effects of DL-alpha-methylornithine on proliferation and polyamine content of 9L rat brain tumor cells.
Treatment of 9L rat brain tumor cells with 10 mM DL-alpha-methylornithine (alpha MO) resulted in cytostasis when cells were plated in monolayer culture at an initial cell density of 5 x 10(5)/flask but not 1 x 10(6). Fifty mM caused cytostasis at both initial densities but more effectively at the lower one. Cytocidal effects measured by a colony-forming efficiency assay were observed at 100 mM but not at 75 mM or less. Both concentrations at both initial cell densities depleted intracellular putrescine content to less than 5% of control by 12 hr and spermidine content to less than 20% of control by 48 hr posttreatment. Intracellular spermine content increased between 1.5- and 2-fold with either concentration of alpha MO and at both densities. Flow cytometry revealed no differences in cell cycle distribution between controls and cells treated with 10 mM alpha MO. The cytostatic effect of 10 mM alpha MO on 9L cultures of lower initial density appeared to be a specific result of polyamine depletion since it was reversible by exogenous putrescine added 24 hr after treatment. The effect of 50 mM alpha MO was not reversible by exogenous putrescine or pyridoxal added simultaneously or 24 hr after treatment. Treatment of 9L cells with 50 mM DL-or L-ornithine caused growth inhibition equal to that produced by 50 mM alpha MO. The effect of 50 mM alpha MO is thus not attributable to polyamine depletion.
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D013096:Spermine; C025025:alpha-methylornithine; D009952:Ornithine; D002262:Carboxy-Lyases; D013095:Spermidine; D011700:Putrescine