The effect of
5-fluorouracil (
5FU) on the 31P nuclear magnetic resonance (NMR) profile of a mouse mammary
carcinoma, implanted on the foot of CH3/He mice, was studied both in vivo and in
perchloric acid extracts. In vivo, significant increases in the ratios,
nucleotide triphosphate:
inorganic phosphate (Pi) (p < 0.02) and
phosphocreatine:Pi (p < 0.005), were observed 48 h after
5FU, relative to control. Two readily resolvable peaks were observed in the phosphomonoester region of the in vivo NMR spectrum,
phosphocholine (PC) and a peak (denoted PME') comprised of mainly
phosphoethanolamine (PE). PME':PC was significantly elevated relative to control from 24 h to 168 h (p < 0.0001 at 48 h).
Perchloric acid extract data indicate that the change in this ratio was due to an increase in the PE concentration rather than a decrease in PC. PE increased from 0.56 +/- 0.11 micromol/g tissue in controls to 0.95 +/- 0.29 micromol/g tissue 48 h after
5FU (p < 0.006).
Perchloric acid extracts also revealed a significant increase in phosphodiesters. Glycerophosphocholine increased from 0.82 +/- 0.24 micromol/g tissue in controls to 1.82 +/- 0.61 micromol/g tissue in
5FU treated
tumors after 48 h (p < 0.002), and
glycerophosphoethanolamine increased from 0.25 +/- 0.06 micromol/g tissue in controls to 0.36 +/- 0.10 micromol/g tissue in treated
tumors (p < 0.004). These changes suggest that
ethanolamine and
choline containing metabolites in this
tumor may be metabolized via different pathways. Cell cycle analysis showed only relatively small changes in cell cycle distribution and apoptotic fraction following
5FU.