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Cyclophosphamide Treatment Modifies Tumor Oxygenation and Glycolytic Rates of RIF-1 Tumors

¹³C Magnetic Resonance Spectroscopy, Eppendorf Electrode, and Redox Scanning

¹ Departments of Radiology,
² Radiation Oncology, and
³ Pathology and
⁴ Johnson Research Foundation, University of Pennsylvania, Philadelphia, Pennsylvania

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 [3-¹³C]lactate after tail vein infusion of labeled [1-¹³C]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 pO₂, 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 pO₂ 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.

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