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

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