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 |
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