In vivo and ex vivo study of metabolic and cellular effects of 5- fluorouracil chemotherapy in a mouse mammary carcinoma

James C. Street, Alan A. Alfieri, Frank Traganos, Jason A. Koutcher

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The effect of 5-fluorouracil (5FU) on the 31P nuclear magnetic resonance (NMR) profile of a mouse mammary carcinoma, implanted on the foot of CH3/He mice, was studied both in vive and in perchloric acid extracts. In vivo, significant increases in the ratios, nucleotide triphosphate:inorganic phosphate (P1) (p < 0.02) and phosphocreatine:P1 (p < 0.005), were observed 48 h after 5FU, relative to control. Two readily resolvable peaks were observed in the phosphomonoester region of the in vive NMR spectrum, phosphocholine (PC) and a peak (denoted PME') comprised of mainly phosphoethanolamine (PE). PME':PC was significantly elevated relative to control from 24 h to 168 h (p < 0.0001 at 48 h). Perchloric acid extract data indicate that the change in this ratio was due to an increase in the PE concentration rather than a decrease in PC. PE increased from 0.56 ± 0.11 μmol/g tissue in controls to 0.95 ± 0.29 μmol/g tissue 48 h after 5FU (p < 0.006). Perchloric acid extracts also revealed a significant increase in phosphodiesters. Glycerophosphocholine increased from 0.82 ± 0.24 μmol/g tissue in controls to 1.82 ± 0.61 μmol/g tissue in 5FU treated tumors after 48 h (p < 0.002), and glycerophosphoethanolamine increased from 0.25 ± 0.06 μmol/g tissue in controls to 0.36 ± 0.10 μmol/g tissue in treated tumors (p < 0.004). These changes suggest that ethanolamine and choline containing metabolites in this tumor may be metabolized via different pathways. Cell cycle analysis showed only relatively small changes in cell cycle distribution and apoptotic fraction following 5FU.

Original languageEnglish (US)
Pages (from-to)587-596
Number of pages10
JournalMagnetic Resonance Imaging
Volume15
Issue number5
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

Chemotherapy
chemotherapy
Fluorouracil
mice
cancer
Tissue
Breast Neoplasms
Drug Therapy
perchloric acid
Phosphorylcholine
Tumors
tumors
Acids
Cell Cycle
Magnetic Resonance Spectroscopy
Cells
Nuclear magnetic resonance
Ethanolamines
choline
Neoplasms

Keywords

  • 5-fluorouracil
  • NMR
  • Phosphocholine
  • Phosphodiester
  • Phosphomonoester
  • Tumor

ASJC Scopus subject areas

  • Biophysics
  • Clinical Biochemistry
  • Structural Biology
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

Cite this

In vivo and ex vivo study of metabolic and cellular effects of 5- fluorouracil chemotherapy in a mouse mammary carcinoma. / Street, James C.; Alfieri, Alan A.; Traganos, Frank; Koutcher, Jason A.

In: Magnetic Resonance Imaging, Vol. 15, No. 5, 1997, p. 587-596.

Research output: Contribution to journalArticle

Street, James C. ; Alfieri, Alan A. ; Traganos, Frank ; Koutcher, Jason A. / In vivo and ex vivo study of metabolic and cellular effects of 5- fluorouracil chemotherapy in a mouse mammary carcinoma. In: Magnetic Resonance Imaging. 1997 ; Vol. 15, No. 5. pp. 587-596.
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