Effect of 6-aminonicotinamide on the pentose phosphate pathway: (31)P NMR and tumor growth delay studies Journal Article
| Authors: | Koutcher, J. A.; Alfieri, A. A.; Matei, C.; Meyer, K. L.; Street, J. C.; Martin, D. S. |
| Article Title: | Effect of 6-aminonicotinamide on the pentose phosphate pathway: (31)P NMR and tumor growth delay studies |
| Abstract: | 6-aminonicotinamide (6AN) has been shown to enhance radiosensitivity in vitro, although previous in vivo studies failed to show an effect. 31P 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 beak 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 x 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 x 3), radiation alone (15 Gy x 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. |
| Keywords: | controlled study; treatment outcome; nonhuman; cancer radiotherapy; radiation dose; combined modality therapy; adenocarcinoma; animals; mice; animal model; drug effect; cancer model; breast carcinoma; magnetic resonance spectroscopy; neoplasm transplantation; tumor growth; radiosensitizing agent; phosphate; phosphorus nuclear magnetic resonance; radiosensitization; mammary neoplasms, experimental; teratogens; nmr; creatine phosphate; pentose phosphate; 6 aminonicotinamide; phosphorus radioisotopes; phosphate metabolism; female; article; 6-aminonicotinamide; pentose phosphate pathway; 6-phosphogluconate; gluconates |
| Journal Title: | Magnetic Resonance in Medicine |
| Volume: | 36 |
| Issue: | 6 |
| ISSN: | 0740-3194 |
| Publisher: | John Wiley & Sons |
| Date Published: | 1996-12-01 |
| Start Page: | 887 |
| End Page: | 892 |
| Language: | English |
| PUBMED: | 8946354 |
| PROVIDER: | scopus |
| DOI: | 10.1002/mrm.1910360611 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work