The inhibitory effects of 5-fluorouracil on the metabolism of preribosomal and ribosomal RNA in L-1210 cells in vitro.

Abstract

Addition of 5FU to the culture medium of mouse L-1210 cells resulted in inhibition of the maturation process of ribosomal RNA precursors in vitro. In the presence of 10(-6) M 5FU for 2 h, the 45S preribosomal RNA was processed to 32S preribosomal RNA, but 28S rRNA was not produced. The processing to 18S rRNA was intact at this drug concentration. Higher concentrations of 5FU for a longer incubation period affected the RNA processing more severely. At 10(-5) M of the drug for 24 h the processing to 28S rRNA and 32S preribosomal RNA. When the cells were labeled with 14C-UR for 2 h following 3H-5FU at 10(-6) M for 24 h, the radioactivities of newly synthesized RNA labeled with 14C-UR accumulated in the region of 45S and 32S preribosomal RNA, and no processing to 28S rRNA was observed. Radioactivity corresponding to 3H-5FU did not persist in the preribosomal RNA region, because further maturation proceeded in the condition of depletion of 5FU after the long incubation period. Thus, inhibition of the processing of preribosomal RNA to 28S rRNA was not brought about by the accumulation of 5FU-substituted 45S preribosomal RNA, but by some other, yet unknown, mechanism.