In vivo and in vitro studies of cyclophosphamide chemotherapy in a mouse mammary carcinoma by 31 P NMR spectroscopy

The effect of cyclophosphamide on the metabolic profile of a mammary carcinoma implanted on the foot of mouse was studied by 31 P NMR spectroscopy both in vivo and in perchloric acid extracts. The ratio nucleotide triphosphate: P i was significantly elevated in cyclophosphamide treated tumours relative to untreated tumours after 96 h in vivo (p<0.05). Phosphocreatine: P i was similarly elevated from 48 to 168 h (p<0.01). Resolution of the phosphomonoester peak into two distinct resonances allowed us to estimate the ratio of PME′ to phosphocholine (PC), where PME′ is a composite peak consisting, in part, of phosphoethanolamine (PE). PME′:PC was found to be significantly higher in treated animals relative to control animals in vivo (p<0.01 from 48 to 168h). Perchloric acid extract spectra suggest that the increase in PME′:PC was in part due to a decrease in PC concentration and also due to an increase in a previously unidentified resonance which was coresonant with PE. Extract data show that there was a significant increase in the concentration of the phosphodiesters, glycerophosphocholine (p<0.01) and glycerophosphoethanolamine (p<0.05) in treated relative to control tumours. The changes in the phosphomonoester resonances are qualitatively similar to previously described changes following radiation and suggest that they may be a marker of cell kill or lack of cell growth after antineoplastic therapy.