In vivo detection by (31)P NMR of pentose phosphate pathway block secondary to biochemical modulation Journal Article
| Authors: | Mahmood, U.; Street, J. C.; Matei, C.; Ballon, D.; Martin, D. S.; Koutcher, J. A. |
| Article Title: | In vivo detection by (31)P NMR of pentose phosphate pathway block secondary to biochemical modulation |
| Abstract: | The chemotherapeutic regimen of N-(phosphonacetyl)-L-aspartate (PALA) followed 17 h later by 6-methylmercaptopurine riboside (MMPR) and 6- aminonicotanamide (6AN) has been shown to be a potent sensitizer of anti- neoplastic therapy. We undertook this study to compare the therapeutic and metabolic effects of this triple drug combination vs one of its components, 6AN, in a murine mammary carcinoma. After treatment with PALA, MMPR and 6AN, a new peak was detected which was assigned to 6-phosphogluconate (6PG), which is a marker of inhibition of the pentose phosphate pathway at the 6- phosphogluconate dehydrogenase step. Treatment with PALA, MMPR and 6AN also induced a decrease in the ratios of nucleoside triphosphate/inorganic phosphate (NTP/P(i)) and phosphocreatine/inorganic phosphate (PCr/P(i)) similar to previous results with a different tumor model. These effects were most pronounced at 6 and 10 h. In addition, an increase in PME'/phosphocholine (PME'=downfield peak in the phosphomonoester region) was detected, which was expected because of the cytotoxic effect of this regimen. Treatment with 6AN alone also resulted in the detection of 6PG with a maximum intensity at 6 h post-6AN. Treatment with 6AN alone induced a smaller change in PME'/PC and failed to cause a decrease in PCr/P(i) or NTP/P(i) at 6 and 10 h. The enhanced response to the combination of PALA, MMPR and 6AN vs 6AN alone, both with regard to cytotoxicity and radiosensitization, may be due to energy depletion. |
| Keywords: | comparative study; methodology; antineoplastic agent; mouse; animal; metabolism; animals; mice; cell division; antineoplastic combined chemotherapy protocols; drug effect; drug derivative; murinae; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; experimental neoplasm; aspartic acid; mammary neoplasms, experimental; teratogens; phosphorus; mice, inbred c3h; phosphonoacetic acid; teratogenic agent; pentose phosphate cycle; c3h mouse; sparfosic acid; 6 aminonicotinamide; male; article; methylthioinosine; 6 methylthioinosine; 6-aminonicotinamide; pentose phosphate pathway |
| Journal Title: | NMR in Biomedicine |
| Volume: | 9 |
| Issue: | 3 |
| ISSN: | 0952-3480 |
| Publisher: | John Wiley & Sons |
| Date Published: | 1996-05-01 |
| Start Page: | 114 |
| End Page: | 120 |
| Language: | English |
| DOI: | 10.1002/(sici)1099-1492(199605)9:3<114::aid-nbm413>3.0.co;2-o |
| PUBMED: | 8892397 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Export Date: 22 November 2017 -- Source: Scopus |
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