5-fluorouridine-5--triphosphate and Carcinoma--Ehrlich-Tumor

Quantitative analysis of extracts from two Ehrlich ascites tumour cell lines (Lettre cells) by 19F NMR in vitro demonstrated that one Lettre cell line (designated LLM) metabolized 30-50% less 5-fluorouracil to 5-fluoronucleotides when compared to the other cell line (designated LHM). HPLC analysis of these cellular extracts showed a significant decrease in the concentration of the cytotoxic nucleotide 5-fluorouridine triphosphate in LLM cells compared to LHM cells. No major differences could be observed in the 31P and 1H NMR spectra of the two cell lines. Growth inhibition studies in vitro demonstrated that LLM cells were less sensitive to 5-fluorouracil than LHM cells. These results are consistent with the hypothesis that 19F NMR visible levels of 5-fluoronucleotides can predict the cytotoxicity of the anti-cancer drug 5-fluorouracil.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Carcinoma, Ehrlich Tumor; Cell Extracts; Chromatography, High Pressure Liquid; Fluorodeoxyuridylate; Fluorouracil; Magnetic Resonance Spectroscopy; Phosphorus; Protons; Tumor Cells, Cultured; Uracil Nucleotides; Uridine Diphosphate Glucose; Uridine Triphosphate

The nucleoside analogues fluorouridine and fluorodeoxyuridine (both at 100 muM) and 8-azaguanine (at 500 muM) inhibit both rRNA transcription and processing in Ehrlich ascites cells. In BHK21 cells fluorodeoxyuridine has no effect on either rRNA maturation or transcription, whereas toyocamycin (at 2 microM) inhibits both processes in BHK21 cells and Ehrlich ascites cells. The drugs inhibit transcription in cells incubated in the complete medium, but have no effect on the decreased transcription in cells incubated in a medium without amino acids. This lack of effect cannot be explained by an altered uptake of the drugs in the amino acid-starved cells, since maturation of the rRNA precursor is affected in cells incubated in media with or without amino acids. The effect of the drugs on rRNA transcription is not the consequence of the inhibition of protein synthesis. The results lend support to the proposal that rRNA processing and transcription are co-ordinately controlled in cells with a high rate of rRNA synthesis.

Topics: Animals; Azaguanine; Carcinoma, Ehrlich Tumor; Cells, Cultured; Cricetinae; Floxuridine; Kidney; Ribosomal Proteins; RNA, Ribosomal; Toyocamycin; Transcription, Genetic; Uracil Nucleotides; Uridine; Uridine Triphosphate