Inhibitors of polyamine biosynthesis. 4. Effects of alpha-methyl-(+/-)-ornithine and methylglyoxal bis(guanylhydrazone) on growth and polyamine content of L1210 leukemic cells of mice

Abstract

L1210 leukemic cells of mice were incubated for a period of two generations in the presence of either alpha-methyl-(+/-)-ornithine, an inhibitor of ornithine decarboxylase, or methylglyoxal bis(guanylhydroazone), an inhibitor of S-adenosylmethionine decarboxylase. alpha-Methyl-(+/-)-ornithine produced a 50% decrease in spermidine levels, reduced putrescine to nondetectable levels, and caused a slight increase in spermine levels of the cells. However, DNA content of the cell suspension was not altered by alpha-methyl-(+/-) ornithine. Thus putrescine and 50% of the cellular content of spermidine are not essential for DNA synthesis in these cells. Methylglyoxal bis(guanylhydrazone) produced a large increase inputrescine levels, the same decrease in spermidine levels as did alpha-methyl-(+/-)-ornithine, and approximately a 45% decrease in spermine levels. These changes were accompanied by a large decrease in the DNA content of the cell suspension. Since the two inhibitors caused a similar decrease in spermidine levels, it is unlikely that the inhibition of DNA synthesis by methylglyoxal bis(guanylhydrazone) is a result of a decrease in the cellular levels of spermidine. Rather, it seems likely that methylglyoxal bis(guanylhydrazone) inhibits DNA synthesis through a mechanism other than a decrease in polyamine levels.