Quantitation of metabolic and radiobiological effects of 6-aminonicotinamide in RIF-1 tumor cells in vitro Journal Article


Authors: Street, J. C.; Alfieri, A. A.; Koutcher, J. A.
Article Title: Quantitation of metabolic and radiobiological effects of 6-aminonicotinamide in RIF-1 tumor cells in vitro
Abstract: 6-Aminonicotinamide (6AN) can be metabolized to 6-amino-NAD(P+), a competitive inhibitor of NAD(P+)-requiring processes, especially the pentose phosphate pathway (PPP) enzyme, 6-phosphogluconate dehydrogenase. The effect of 6AN on the flux of 1 and 6 13C-labeled glucose to lactate, via glycolysis and the PPP, was investigated using 1H-nuclear magnetic resonance. These studies showed that 6AN as a single agent caused a significant 89% (P < 0.0001) inhibition of glycolytic flux but had no detectable effect on the PPP. 31P-nuclear magnetic resonance studies of perifused RIF-1 cells indicated that 4 h of exposure to 6AN were sufficient to cause significant accumulation of 6-phosphogluconate, the substrate for this enzyme (P < 0.0001). A significant reduction in the phosphocreatine: inorganic phosphate ratio was observed under conditions that led to accumulation of 6-phosphogluconate (P < 0.006). Accumulation of 6- phosphogluconate and subsequent reduction in phosphocreatine correlated with significant potentiation of 6 Gy of irradiation by 6AN. These results suggest that the radiation enhancement effect of 6AN may be due to inhibition of glycolysis (mediated by 6-phosphogluconate) and the associated reduction in high-energy phosphates. Additional studies analyzing the metabolic effects of 6AN in combination with radiation are necessary to determine the role of inhibition of the PPP in 6AN enhancement of radiation.
Keywords: nonhuman; quantitative assay; animal cell; dna repair; enzyme inhibition; drug effect; tumor cells, cultured; irradiation; tumor cell; magnetic resonance spectroscopy; drug metabolism; radiation-sensitizing agents; phosphate; glycolysis; proton nuclear magnetic resonance; radiobiology; competitive inhibition; creatine phosphate; gamma rays; phosphocreatine; 6 aminonicotinamide; lactates; high energy phosphate; priority journal; article; 6-aminonicotinamide; pentose phosphate pathway
Journal Title: Cancer Research
Volume: 57
Issue: 18
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 1997-09-01
Start Page: 3956
End Page: 3962
Language: English
PUBMED: 9307279
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Jason A Koutcher
    278 Koutcher
  2. Alan A. Alfieri
    35 Alfieri
  3. James C. Street
    10 Street