31P NMR spectroscopic studies of the effects of cyclophosphamide on perfused RIF-1 tumor cells.
To determine whether direct cellular effects of chemotherapy are responsible for 31P NMR spectral changes observed in treated tumors in vivo, RIF-1 fibrosarcoma cells were examined in vitro before, during, and after treatment with 4-hydroperoxycyclophosphamide (4-HC), an activated form of cyclophosphamide. When RIF-1 cells were treated with 4-HC in a metabolically stable but nonproliferating state, the 31P NMR spectra were identical with those of untreated cells for up to 70 h. When actively proliferating RIF-1 cells were treated with 4-HC, the intensities of the nucleotide triphosphate resonances, which increased linearly during control cell growth, remained constant for 50 h or longer. These studies demonstrate that the bioenergetic improvement observed following treatment of RIF-1 tumors in vivo [S.-J. Li, J.P. Wehrle, S.S. Rajan, R.G. Steen, J.D. Glickson, and J. Hilton, Cancer Res. 48, 4736 (1988)] does not result from direct effects of cyclophosphamide metabolites on RIF-1 cell metabolism, but rather from indirect effects of treatment on tumor or host physiology.
Aiken
N R
NR
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
McGovern
K A
KA
Ng
C E
CE
Wehrle
J P
JP
Glickson
J D
JD
D000818:Animals; D002455:Cell Division; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005354:Fibrosarcoma / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010759:Phosphorus Isotopes; D014407:Tumor Cells, Cultured
D010759:Phosphorus Isotopes; D003520:Cyclophosphamide; C011272:perfosfamide