Nonglycolytic acidification of murine radiation-induced fibrosarcoma 1 tumor via 3-O-methyl-D-glucose monitored by 1H, 2H, 13C, and 31P nuclear magnetic resonance spectroscopy.

Abstract

The effects of 3-O-methyl-D-glucose (3-OMG) on subcutaneously implanted murine radiation-induced fibrosarcoma 1 tumor were examined with 2H, 13C, and 31P nuclear magnetic resonance (NMR) in situ. Using 31P NMR, changes in tumor high-energy phosphate metabolism were monitored for 2.5 h after i.p. administration of 3-OMG (8.1 g/kg body weight); tumor pH decreased by a mean maximum of 0.52 +/- 0.05 (SE) (n = 10), [PCr] decreased by 54%, [NTP] decreased by 35%, and [Pi] increased by 36%. Tumor blood flow, as measured by 2H NMR monitoring of D2O washout kinetics, decreased by 40% at 1 h and by 47% at 2 h after 3-OMG injection (n = 4). This substantial tumor acidification (pH decrease much greater than 0.1), expected to require a glycolytic substrate (Hwang et al., Cancer Res., 51: 3108-3118, 1991), is surprising in light of the previously documented metabolically inert nature of 3-OMG. In situ 13C NMR spectroscopy, following [6-13C]3-OMG i.p. injection, examined the possibility of the glycolytic metabolism of 3-OMG. However, only the C-6 resonance of 3-OMG was detected (n = 6); no resonances from [6-13C]3-OMG-6-phosphate or [3-13C]lactate were observed. These results confirmed that 3-OMG was not metabolized in radiation-induced fibrosarcoma 1 tumor. At the completion of the in situ 13C NMR experiments, tumors were freeze clamped, and perchloric acid extraction was performed. High-resolution 1H NMR measurement of lactate concentrations showed no statistically significant difference in control tumor extracts (from mice not receiving i.p. injection; n = 5) and in tumor extracts from mice administered i.p. [6-13C]3-OMG (n = 5), indicating that there was no significant increase in lactate level in the tumor extracts from mice administered i.p. 3-OMG due to increased plasma glucose concentration. The results of these 1H and 13C NMR studies indicated that the radiation-induced fibrosarcoma 1 tumor acidification caused by i.p. administration of 3-OMG was not due to a direct (3-OMG----lactate) or an indirect (systemic glucose----lactate) increase in tumor lactic acid levels.

• Authors: Y Y Hwang, S G Kim, J L Evelhoch, J J Ackerman
• Journal: Cancer research (Cancer Res) Vol. 52 Issue 5 Pg. 1259-66 (Mar 01 1992) ISSN: 0008-5472 [Print] United States
• PMID: 1737388 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Blood Glucose
• Carbon Radioisotopes
• Lactates
• Methylglucosides
• Nucleosides
• Phosphates
• Phosphocreatine
• 3-O-Methylglucose
• Lactic Acid
• Mannitol
• Deuterium
• Glucose

Topics

• 3-O-Methylglucose
• Animals
• Blood Glucose (metabolism)
• Carbon Radioisotopes
• Deuterium
• Female
• Fibrosarcoma (blood supply, metabolism)
• Glucose (pharmacology)
• Hematocrit
• Hydrogen-Ion Concentration
• Lactates (metabolism)
• Lactic Acid
• Magnetic Resonance Spectroscopy
• Mannitol (pharmacology)
• Methylglucosides (pharmacology)
• Mice
• Mice, Inbred C3H
• Neoplasms, Radiation-Induced (blood supply, metabolism)
• Nucleosides (metabolism)
• Phosphates
• Phosphocreatine (metabolism)