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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1996-6-21
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pubmed:abstractText |
The effect of 6-aminonicotinamide on the metabolism of RIF-1 tumor cells was investigated using 13C and 31P NMR spectroscopy. 6-Aminonicotinamide can be metabolized to 6-amino-NAD(P), a competitive inhibitor of NAD(P)-requiring processes. 40 microM 6-aminonicotinamide led to an inhibition of 6-phosphogluconate dehydrogenase and an accumulation of 6-phosphogluconate. A subsequent accumulation of the 6-phosphogluconate precursor 6-phosphoglucono-delta-lactone was observed in the 13C NMR spectrum. These metabolites were shown to be intracellular, although a small amount of leakage of 6-phosphoglucono-delta-lactone occurred. The intracellular concentrations of 6-phosphogluconate and 6-phosphoglucono-delta-lactone were 1.9 +/- 0.8 micromol/108 cells (+/-1 standard deviation) and 0.8 +/- 0.4 micromol/10(8) cells, respectively, after 15 h. Glucose utilization and lactate production were significantly inhibited by 6-aminonicotinamide (both p < 0.05), indicating inhibition of glycolysis. 31P NMR data showed that phosphocreatine was significantly depleted in cells exposed to 6-aminonicotinamide (p < 0.05). Exposure of RIF-1 cells to 6-aminonicotinamide prior to 3- or 6-Gy x-irradiation induced a supra-additive cell kill, indicating that 6-aminonicotinamide is acting as a radiosensitizer. There was no effect of 6-aminonicotinamide alone or when the drug was given postradiation, suggesting that its mechanism of action may be by inhibition of radiation-induced repair.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
271
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4113-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8626749-6-Aminonicotinamide,
pubmed-meshheading:8626749-Animals,
pubmed-meshheading:8626749-Carbon Isotopes,
pubmed-meshheading:8626749-Cell Line,
pubmed-meshheading:8626749-Cell Survival,
pubmed-meshheading:8626749-Dose-Response Relationship, Drug,
pubmed-meshheading:8626749-Fibrosarcoma,
pubmed-meshheading:8626749-Glucose,
pubmed-meshheading:8626749-Glycolysis,
pubmed-meshheading:8626749-Kinetics,
pubmed-meshheading:8626749-Magnetic Resonance Spectroscopy,
pubmed-meshheading:8626749-Neoplasms, Radiation-Induced,
pubmed-meshheading:8626749-Phosphorus,
pubmed-meshheading:8626749-Time Factors,
pubmed-meshheading:8626749-Tumor Cells, Cultured,
pubmed-meshheading:8626749-X-Rays
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pubmed:year |
1996
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pubmed:articleTitle |
13C and 31P NMR investigation of effect of 6-aminonicotinamide on metabolism of RIF-1 tumor cells in vitro.
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pubmed:affiliation |
Department of Medical Physics, Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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