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

Abstract
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.
AuthorsJ C Street, U Mahmood, C Matei, J A Koutcher
JournalNMR in biomedicine (NMR Biomed) Vol. 8 Issue 4 Pg. 149-58 (Jun 1995) ISSN: 0952-3480 [Print] England
PMID8771089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents, Alkylating
  • Phosphates
  • Phospholipids
  • Phosphorus Isotopes
  • Cyclophosphamide
Topics
  • Adenocarcinoma (drug therapy, metabolism)
  • Animals
  • Antineoplastic Agents, Alkylating (pharmacology)
  • Cyclophosphamide (pharmacology)
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Magnetic Resonance Spectroscopy (methods)
  • Mammary Neoplasms, Experimental (drug therapy, metabolism)
  • Mice
  • Mice, Inbred C3H
  • Neoplasm Transplantation
  • Phosphates (metabolism)
  • Phospholipids (metabolism)
  • Phosphorus Isotopes

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