Regulation of ribosomal RNA synthesis and processing during inhibition of protein synthesis by 1,3-bis(2-chloroethyl)-1-nitrosourea

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Abstract
The antineoplastic agent BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) at a concentration of 25 .mu.g/ml inhibits initiation of protein synthesis in HeLa [human cervical cancer] cells. At this low concentration of the drug, the rate of synthesis of 45S precursor rRNA (pre-rRNA) is selectively inhibited without a marked inhibition of nucleoplasmic RNA. The inhibitory effects of the drug are readily reversible on removal of BCNU from the growth medium. Pulse chase analysis of the labeled nucleolar RNA in sucrose gradients and acrylamide gels indicated that the 45S pre-rRNA synthesized before the addition of BCNU matures normally in the presence of the inhibitor. The processing of precursor RNA molecules synthesized following the addition of the drug is inhibited when incubation is continued in the presence of 25 .mu.g/ml BCNU. Since the formation of mature ribosomes is blocked by BCNU, the data would suggest that the effectiveness of the drug as a potent cell growth inhibitor may result from its inhibition of ribosome formation induced by inhibition of protein synthesis.

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