13C and 31P NMR investigation of effect of 6-aminonicotinamide on metabolism of RIF-1 tumor cells in vitro. Academic Article uri icon

Overview

MeSH

  • Animals
  • Carbon Isotopes
  • Cell Line
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Fibrosarcoma
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Neoplasms, Radiation-Induced
  • Phosphorus
  • Time Factors
  • Tumor Cells, Cultured
  • X-Rays

MeSH Major

  • 6-Aminonicotinamide
  • Glucose
  • Glycolysis

abstract

  • 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.

publication date

  • February 23, 1996

has subject area

  • 6-Aminonicotinamide
  • Animals
  • Carbon Isotopes
  • Cell Line
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Fibrosarcoma
  • Glucose
  • Glycolysis
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Neoplasms, Radiation-Induced
  • Phosphorus
  • Time Factors
  • Tumor Cells, Cultured
  • X-Rays

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 8626749

Additional Document Info

start page

  • 4113

end page

  • 4119

volume

  • 271

number

  • 8