QUANTITATION OF METABOLIC AND RADIOBIOLOGICAL EFFECTS OF 6-AMINONICOTINAMIDE IN RIF-1 TUMOR-CELLS IN-VITRO

6-Aminonicotinamide (6AN) can be metabolized to 6-amino-NAD(P+), a com petitive inhibitor of NAD(P+)-requiring processes, especially the pent ose phosphate pathway (PPP) enzyme, 6-phosphogluconate dehydrogenase, The effect of 6AN on the flux of 1 and 6 C-13-labeled glucose to lacta te, via glycolysis and the PPP, was investigated using H-1-nuclear mag netic resonance, These studies showed that 6AN as a single agent cause d a significant 89% (P < 0.0001) inhibition of glycolytic flux but had no detectable effect on the PPP, P-31-nuclear magnetic resonance stud ies of perifused RIF-1 cells indicated that 4 h of exposure to 6AN wer e 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 con ditions that led to accumulation of 6-phosphogluconate (P < 0.006), Ac cumulation of 6-phosphogluconate and subsequent reduction in phosphocr eatine correlated with significant potentiation of 6 Gy of irradiation by 6AN, These results suggest that the radiation enhancement effect o f 6AN may be due to inhibition of glycolysis (mediated by 6-phosphoglu conate) and the associated reduction in high-energy phosphates, Additi onal studies analyzing the metabolic effects of 6AN in combination wit h radiation are necessary to determine the role of inhibition of the P PP in 6AN enhancement of radiation.