Detection of differential sensitivity to 5-fluorouracil in Ehrlich ascites tumour cells by 19F NMR spectroscopy.
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.
McSheehy
P M
PM
Department of Cellular & Molecular Sciences, St George's Hospital Medical School, London, UK.
Maxwell
R J
RJ
Griffiths
J R
JR
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002457:Cell Extracts / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D005468:Fluorodeoxyuridylate / Q000031:analogs & derivatives / Q000378:metabolism; D005472:Fluorouracil / Q000378:metabolism* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010758:Phosphorus; D011522:Protons; D014407:Tumor Cells, Cultured; D014500:Uracil Nucleotides / Q000378:metabolism; D014532:Uridine Diphosphate Glucose / Q000031:analogs & derivatives / Q000378:metabolism; D014544:Uridine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism
D002457:Cell Extracts; D011522:Protons; D014500:Uracil Nucleotides; D005468:Fluorodeoxyuridylate; D010758:Phosphorus; C025635:5-fluorouridine 5'-triphosphate; D000244:Adenosine Diphosphate; C049358:5-fluorouridine diphosphate glucose; D000255:Adenosine Triphosphate; D005472:Fluorouracil; D014544:Uridine Triphosphate; D014532:Uridine Diphosphate Glucose