DETECTION OF DIFFERENTIAL SENSITIVITY TO 5-FLUOROURACIL IN EHRLICH ASCITES TUMOR-CELLS BY F-19 NMR-SPECTROSCOPY

Quantitative analysis of extracts from two Ehrlich ascites tumour cell lines (Lettre cells) by F-19 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 P-31 and H-1 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 F-19 NMR visible levels of 5-fluoronucleotides can predict the cytotoxicity of the anti-cancer drug 5-fluorouracil.