Nonglycolytic Acidification of Murine Radiation-induced Fibrosarcoma 1 Tumor via 3-O-Methyl-D-glucose Monitored by *H, 2H, 13C, and 31P Nuclear Magnetic Resonance Spectroscopy

Yuying C. Hwang, Seong Gi Kim, Joseph J.H. Ackerman

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Abstract

The effects of 3-O-methyl-D-glucose (3-OMG) on subcutaneously implanted murine radiation-induced fibrosarcoma 1 tumor were examined with 2H, “C, and 3,P nuclear magnetic resonance (NMR) in situ. Using 31P NMR, changes in tumor high-energy phosphate metabolism were monitored for IS 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 |P,| increased by 36%. Tumor blood flow, as measured by 2H NMR monitoring of D20 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 “0.1), expected to require a glycolytic substrate (Hwang et aL, Cancer Res., 51: 3108-3118, 199IX is surprising in light of the previously documented metabolically inert nature of 3-OMG. In situ 13C NMR spectroscopy, following [6-l3C|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 (it = 6); no resonances from [6-13CP-OMG-6-phosphate or |3-13qiactate were observed. These results confirmed that 3-OMG was not metabolized in radiation-induced fibrosarcoma 1 tumor. At the completion of the in situ, 3C NMR experiments, tumors were freeze clamped, and perchloric acid extraction was performed. High-resolution 'H 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 (it = 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 'H and, 3C 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.

Original languageEnglish
Pages (from-to)1259-1266
Number of pages8
JournalCancer research
Volume52
Issue number5
StatePublished - Mar 1992

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