Early metabolic response to tumor necrosis factor in mouse sarcoma: a phosphorus-31 nuclear magnetic resonance study

To investigate the effects of recombinant human tumor necrosis factor alpha (rHuTNF-alpha) on high-energy phosphate metabolism of cancer cells, 31P nuclear magnetic resonance (NMR) studies were performed on a murine methylcholanthrene-induced sarcoma. Injection of 15 micrograms of rHuTNF-alpha cause...

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Published inCancer research (Chicago, Ill.) Vol. 49; no. 8; pp. 2123 - 2127
Main Authors SHINE, N, PALLADINO, M. A. JR, PATTON, J. S, DEISSEROTH, A, KARCZMAR, G. S, MATSON, G. B, WEINER, M. W
Format Journal Article
LanguageEnglish
Published Philadelphia, PA American Association for Cancer Research 15.04.1989
Subjects
Adenosine Triphosphate - analysis
Animals
Biological and medical sciences
Female
Magnetic Resonance Spectroscopy
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Other treatments
Phosphates - analysis
Phosphocreatine - analysis
Recombinant Proteins - pharmacology
Sarcoma, Experimental - metabolism
Treatment. General aspects
Tumor Necrosis Factor-alpha - pharmacology
Tumors
Phosphates
Vertebrata
Mammalia
Treatment
Ischemia
Sarcoma
Mouse
Tumor necrosis factor
Rodentia
NMR spectrometry
Metabolism
Experimental tumor
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Summary:To investigate the effects of recombinant human tumor necrosis factor alpha (rHuTNF-alpha) on high-energy phosphate metabolism of cancer cells, 31P nuclear magnetic resonance (NMR) studies were performed on a murine methylcholanthrene-induced sarcoma. Injection of 15 micrograms of rHuTNF-alpha caused progressive depletion of ATP and phosphocreatine within 90 min, together with an increase in inorganic phosphate. Metabolic changes were correlated with the early histological appearance of thrombosis and hemorrhage. A spatially localized NMR technique demonstrated that these changes were specific for the tumor. Acute ischemia of the tumor produced similar metabolic changes; thus the metabolic effects of rHuTNF-alpha could be due to either a primary action on tumor biochemistry or a secondary action produced by ischemia. These findings indicate that rHuTNF-alpha has a very rapid onset of action, which can be detected by 31P NMR. Furthermore, the results suggest that 31P NMR spectroscopy will be extremely useful for detecting early biochemical changes produced by rHuTNF-alpha or other treatments in animal and human cancers.
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ISSN:0008-5472
1538-7445