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
L1210 leukemic cells of mice were incubated for a period of 2 generations in the presence of either .alpha.-methyl-(.+-.)-ornithine, an inhibitor of ornithine decarboxylase, or methylglyoxal bis(guanylhydrazone), 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. DNA content of the cell suspension was not altered by .alpha.-methyl-(.+-.)-ornithine. 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 in putrescine 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 2 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. It seems likely that methylglyoxal bis(guanylhydrazone) inhibits DNA synthesis through a mechanism other than a decrease in polyamine levels.