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Effect of 6‐aminonicotinamide on the pentose phosphate pathway: 31 P NMR and tumor growth delay studies
Author(s) -
Koutcher Jason A.,
Alfieri Alan A.,
Matei Cornelia,
Meyer Kristen L.,
Street James C.,
Martin Daniel S.
Publication year - 1996
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.1910360611
Subject(s) - pentose phosphate pathway , chemistry , phosphate , nuclear magnetic resonance spectroscopy , radiochemistry , metabolism , nuclear magnetic resonance , biochemistry , glycolysis , stereochemistry , physics
6‐aminonicotinamide (6AN) has been shown to enhance radio‐sensitivity in vitro , although previous in vivo studies failed to show an effect. 31 P NMR spectra were obtained by using a one‐dimensional chemical shift imaging technique on a first generation transplant of the CD8FI spontaneous mammary carcinoma tumor model. Spectra were obtained both before and 10 h after treatment with 6AN (20 mg/kg). Changes in pH, nucleoside triphosphate/inorganic phosphate, and phosphocreatine/inorganic phosphate measured at 10 h post‐6AN were not significant. A new peak was detected 10 h post‐6AN, which was assigned to 6‐phosphogluconate (6PG), indicating inhibition of the pentose phosphate pathway (PPP). Based on the spectral data demonstrating inhibition of the PPP at 10 h post‐6AN, tumor‐bearing mice were irradiated (15 Gy × 3 fractions) on Days 1, 10 or 11, and 21 10 h after administration of 6‐aminonicotinamide (20 mg/kg). Tumor‐bearing mice receiving 6AN alone (20 mg/kg × 3), radiation alone (15 Gy × 3), or saline were also studied. Tumor growth delay studies indicated that 6AN alone induced a small but significant tumor growth delay (4.3 ± 0.8 days). Radiation alone induced a tumor growth delay of 34.5 ± 2.7 days. Treatment with 6AN followed by radiation induced a tumor growth delay of 57.0 ± 3.8 days. This was significantly greater than the TGD values for treatment with 6AN alone or radiation ( P < 0.01). No complete regressions were noted after treatment with 6AN or radiation alone. Concomitant therapy with 6AN plus radiation yielded 6/28 complete regressions (21%), which was significantly greater than radiation ( P < 0.05) or 6AN alone ( P < 0.01) on this mammary carcinoma.