Cyclophosphamide treatment modifies tumor oxygenation and glycolytic rates of RIF-1 tumors: 13C magnetic resonance spectroscopy, Eppendorf electrode, and redox scanning.
The effect of cyclophosphamide (Cp) on the glycolytic rate of radiation-induced fibrosarcomas (RIF-1) was measured in vivo in C3H mice by following the production of [3-(13)C]lactate after tail vein infusion of labeled [1-(13)C]glucose. Cp administered i.p. at a dose of 300 mg/kg caused a significant drop in glycolytic rate 24 h after treatment (P < 0.01). This drop was accompanied by an increase in [C-3]/[C-4] glutamate ratio in perchloric acid extracts of the tumors, indicating an increase in the Kreb's cycle activity. Treatment with Cp led to a significant decrease (P < 0.01) in tissue pO(2), measured in vivo with an oxygen Eppendorf electrode. Increases in NADH levels were also observed in rapidly frozen excised tumors examined by three-dimensional optical redox scanning. A significant decrease in tumor pO(2) and an increase in the NADH levels are suggestive of an increase in oxygen consumption by these tumors after Cp treatment. Overall, these data indicate that the reduction in glycolytic rate of Cp-treated RIF-1 tumors is due to an increase in aerobic metabolism.
Poptani
Harish
H
Departments of Radiology, Johnson Research Foundation, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. Poptani@oasis.upenn.edu
Bansal
Navin
N
Jenkins
Walter T
WT
Blessington
Dana
D
Mancuso
Anthony
A
Nelson
David S
DS
Feldman
Michael
M
Delikatny
Edward J
EJ
Chance
Britton
B
Glickson
Jerry D
JD
D000818:Animals; D002247:Carbon Isotopes; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D017736:Ion-Selective Electrodes; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D008928:Mitochondria / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D014463:Ultrasonography
D002247:Carbon Isotopes; D018698:Glutamic Acid; D003520:Cyclophosphamide; D010100:Oxygen