Effects of 5-fluorouracil on cytotoxicity and RNA metabolism in human colonic carcinoma cells.
The cytotoxicity of 5-fluorouracil (5-FU) is due in part to the incorporation of the base into RNA molecules. We assessed the cytotoxicity of 5-FU in human colonic carcinoma HT-29 cells and examined mRNA activity (measured by protein biosynthesis in vivo and in vitro) and the maturation of rRNA precursors as two possible modes of action of 5-FU. The rRNA processing pathways were studied using rDNA sequences as probes in blot hybridisation protocols and were specific for both the precursors and mature rRNA species of the maturation pathways. The conclusion from the studies was that although differences in mRNA activity were detected in vivo and in vitro, the significance of these changes are as yet unknown. In contrast, the effects on the pre-rRNA processing pathways proved to be highly significant cytotoxic consequences of 5-FU administration. We discuss the implications of this finding for an understanding of the mode of action of the drug and for the future monitoring of tumour sensitivity to 5-FU.
Greenhalgh
D A
DA
Department of Biochemistry, University of Leeds, UK.
Parish
J H
JH
D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015342:DNA Probes; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000627:therapeutic use / Q000633:toxicity*; D006801:Humans; D015151:Immunoblotting; D009693:Nucleic Acid Hybridization / Q000187:drug effects; D012334:RNA, Neoplasm / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D012335:RNA, Ribosomal / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D015342:DNA Probes; D012334:RNA, Neoplasm; D012335:RNA, Ribosomal; D005472:Fluorouracil