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5-氟尿嘧啶对体外培养的L-1210细胞中原核糖体RNA和核糖体RNA代谢的抑制作用。

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

作者信息

Kanamaru R, Kakuta H, Sato T, Ishioka C, Wakui A

出版信息

Cancer Chemother Pharmacol. 1986;17(1):43-6. doi: 10.1007/BF00299864.

DOI:10.1007/BF00299864
PMID:3698176
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.

摘要

在小鼠L-1210细胞的培养基中添加5-氟尿嘧啶(5FU)可在体外抑制核糖体RNA前体的成熟过程。在存在10⁻⁶ M 5FU的情况下培养2小时,45S核糖体前体RNA被加工成32S核糖体前体RNA,但未产生28S核糖体RNA。在该药物浓度下,向18S核糖体RNA的加工过程未受影响。更高浓度的5FU以及更长的孵育时间对RNA加工的影响更为严重。在10⁻⁵ M该药物作用24小时后,向28S核糖体RNA和32S核糖体前体RNA的加工过程受到影响。当细胞在10⁻⁶ M 3H-5FU作用24小时后用14C-尿嘧啶(14C-UR)标记2小时时,用14C-UR标记的新合成RNA的放射性积聚在45S和32S核糖体前体RNA区域,未观察到向28S核糖体RNA的加工过程。与3H-5FU相对应的放射性在核糖体前体RNA区域未持续存在,因为在长时间孵育后,在5FU耗尽的条件下进一步的成熟过程仍在进行。因此,核糖体前体RNA向28S核糖体RNA加工过程的抑制不是由5FU取代的45S核糖体前体RNA的积累引起的,而是由其他一些未知机制导致的。

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