In vivo and in vitro studies of cyclophosphamide chemotherapy in a mouse mammary carcinoma by 31P NMR spectroscopy.
The effect of cyclophosphamide on the metabolic profile of a mammary carcinoma implanted on the foot of mouse was studied by 31P 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 168 h). 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.
Street
J C
JC
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Mahmood
U
U
Matei
C
C
Koutcher
J A
JA
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D010710:Phosphates / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010759:Phosphorus Isotopes
D018906:Antineoplastic Agents, Alkylating; D010710:Phosphates; D010743:Phospholipids; D010759:Phosphorus Isotopes; D003520:Cyclophosphamide