In vivo detection by 31P NMR of pentose phosphate pathway block secondary to biochemical modulation. Academic Article Article uri icon

Overview

MeSH

  • Animals
  • Aspartic Acid
  • Cell Division
  • Magnetic Resonance Spectroscopy
  • Male
  • Methylthioinosine
  • Mice
  • Mice, Inbred C3H
  • Phosphonoacetic Acid
  • Phosphorus

MeSH Major

  • 6-Aminonicotinamide
  • Antineoplastic Combined Chemotherapy Protocols
  • Mammary Neoplasms, Experimental
  • Pentose Phosphate Pathway
  • Teratogens

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/Pi) and phosphocreatine/inorganic phosphate (PCr/Pi) 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/Pi or NTP/Pi 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.

publication date

  • May 1996

has subject area

  • 6-Aminonicotinamide
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols
  • Aspartic Acid
  • Cell Division
  • Magnetic Resonance Spectroscopy
  • Male
  • Mammary Neoplasms, Experimental
  • Methylthioinosine
  • Mice
  • Mice, Inbred C3H
  • Pentose Phosphate Pathway
  • Phosphonoacetic Acid
  • Phosphorus
  • Teratogens

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1002/(SICI)1099-1492(199605)9:3<114::AID-NBM413>3.0.CO;2-O

PubMed ID

  • 8892397

Additional Document Info

start page

  • 114

end page

  • 120

volume

  • 9

number

  • 3