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PubMed · 3941072

Fluoropyrimidine-mediated changes in small nuclear RNA.

R D Armstrong·C H Takimoto·E C Cadman
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Abstract

Studies were completed to examine the effects of the antineoplastic agent 5-Fluorouridine (FUrd) on the metabolism of the small molecular weight nuclear RNA (snRNA). Cultured Sarcoma-180 murine tumor cells were exposed to FUrd concurrent with [3H]cytidine for 6 h, the drug was removed, and the RNA was isolated at 0, 24, or 48 h following the drug treatment. The results of these studies demonstrated that FUrd produced three dose-dependent changes in snRNA metabolism. The electrophoretic migration of the U4 and U6 snRNA was altered in nondenaturing 10% polyacrylamide slab gels. These results were not observed in denaturing gels or when RNA was extracted at temperatures exceeding 25 degrees C, suggesting that the incorporation of 5-fluorouracil induced secondary structural changes in these RNA. A dose- and time-dependent selective reduction in the turnover of the U1 snRNA synthesized in the presence of FUrd was observed as well, with levels over 100% higher than control cells at 48 h after exposure to 10 microM FUrd. These changes in snRNA metabolism may contribute to the reported alterations in large molecular weight RNA metabolism that also result in fluoropyrimidine-treated cells, or to cytotoxicity.

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AnimalsCell LineCell SurvivalCytidineDose-Response Relationship, DrugElectrophoresis, Polyacrylamide GelMiceNucleic Acid ConformationRNA, Small NuclearSarcoma 180Time FactorsUridineJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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R D Armstrong, C H Takimoto, E C Cadman. 1986-01-05. Fluoropyrimidine-mediated changes in small nuclear RNA.. https://pubmed.ncbi.nlm.nih.gov/3941072/

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