Effect of l-asparaginase and asparagine deprivation on RNA metabolism in mouse leukemia L 5178Y cells in suspension culture.

We analyzed the effect of asparagine starvation and L-asparaginase on RNA metabolism of mouse leukemia cell lines L5178Y, whose growth is dependent on the presence of asparagine, and L5178Y-R, whose growth is independent of the presence of asparagine. The deprivation of asparagine from the medium inhibited cellular protein synthesis by 30 to 40% of the control value in L5178Y cells, but not in L5178Y-R cells, whereas L-asparaginase inhibited synthesis by more than 80% in both L5178Y and L5178Y-R cells. The decrease in protein synthesis caused by asparagine starvation in L5178Y cells was accompanied by a decrease in ribosomal RNA synthesis. The synthesis of rRNA was also markedly blocked when L5178Y and L5178Y-R cells were exposed to L-asparaginase. The rate of synthesis of pulse-labeled RNA decreased significantly in the cells treated with L-asparaginase, and smaller pieces of polyadenylate containing pulse-labeled RNA (presumptive messenger RNA) appeared among monosomes and polysomes. However, the rate of messenger RNA synthesis was constant during asparagine starvation, and a marked accumulation of monosome was observed.