The inhibition of ribosomal RNA synthesis and maturation in Novikoff hepatoma cells by 5-fluorouridine.
The inhibition of ribosomal RNA synthesis and maturation in Novikoff hepatoma cells by 5-fluorouridine.
复制标题
5-氟尿苷对 Novikoff 肝癌细胞核糖体 RNA 合成和成熟的抑制。
作者：
D. Wilkinson;T. Tlsty;R. J. Hanas
5-氟吡啶（FUrd）对诺维科夫肝癌细胞核糖体RNA （rRNA）成熟的抑制作用似乎取决于将类似物掺入45s rRNA前体。在没有类似物存在的情况下合成的前体不会被加工成成熟的rRNA，而在没有类似物存在的情况下合成的前体在加入药物后被正常加工。FUrd对rRNA成熟的影响是浓度依赖性的。在浓度为1 × 10(-4)M时，模拟物完全抑制成熟的18s和28s rRNA的形成；而在浓度为1 × 10(-7)M时，该类似物对rRNA成熟无显著影响。这些结果表明，一定程度的类似物取代是抑制成熟过程所必需的。除了抑制成熟外，FUrd还抑制45s rRNA前体的转录。然而，这种药物的作用是不完全的，更多的时间依赖于成熟的影响。从培养基中去除类似物后，FUrd对rRNA成熟的抑制仍然存在。将药物从培养基中去除20小时后，暴露于FUrd 2小时的细胞无法处理45s rRNA前体。
The inhibition of ribosomal RNA (rRNA) maturation by 5-fluorouridine (FUrd) in Novikoff hepatoma cells appears to depend upon the incorporation of the analog into the 45 S rRNA precursor. Precursor synthesized in the presence of FUrd is not processed into mature rRNA, but precursor synthesized in the absence of the analog is processed normally after the addition of the drug. The effect of FUrd on rRNA maturation is concentration dependent. At a concentration of 1 X 10(-4)M, the analog completely inhibits the formation of mature 18 S and 28 S rRNA; while at a concentration of 1 X 10(-7)M, the analog has no significant effect on rRNA maturation. These results suggest that some minimum degree of analog substitution is necessary to inhibit the maturation process. In addition to its inhibition of maturation, FUrd also inhibits the transcription of 45 S rRNA precursor. However, this effect of the drug is less complete and more time dependent that the effect on maturation. The inhibition of rRNA maturation by FUrd persists after removal of the analog from the culture medium. Cells that had been exposed to FUrd for 2 hr were unable to process 45 S rRNA precursor 20 hr after removal of the drug from the medium.