Quantitation of metabolic and radiobiological effects of 6-aminonicotinamide in RIF-1 tumor cells in vitro.
Cancer Res
; 57(18): 3956-62, 1997 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-9307279
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.
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Base de dados:
MEDLINE
Assunto principal:
Via de Pentose Fosfato
/
Radiossensibilizantes
/
Glicólise
/
6-Aminonicotinamida
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos