Simultaneous administration of glucose and hyperoxic gas achieves greater improvement in tumor oxygenation than hyperoxic gas alone

Stacey A. Snyder, Jennifer L. Lanzen, Rod D. Braun, Gary Rosner, Timothy W. Secomb, John Biaglow, David M. Brizel, Mark W. Dewhirst

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Purpose: To test the feasibility of hyperglycemic reduction of oxygen consumption combined with oxygen breathing (O 2), to improve tumor oxygenation. Methods and Materials: Fischer-344 rats bearing 1 cm R3230Ac flank tumors were anesthetized with Nembutal. Mean arterial pressure, heart rate, tumor blood flow ([TBF], laser Doppler flowmetry), pH, and pO 2 were measured before, during, and after glucose (1 or 4 g/kg) and/or O 2. Results: Mean arterial pressure and heart rate were unaffected by treatment. Glucose at 1 g/kg yielded maximum blood glucose of 400 mg/dL, no change in TBF, reduced tumor pH (0.17 unit), and 3 mm Hg pO 2 rise. Glucose at 4 g/kg yielded maximum blood glucose of 900 mg/dL, pH drop of 0.6 unit, no pO 2 change, and reduced TBF (31%). Oxygen tension increased by 5 mm Hg with O 2. Glucose (1 g/Kg) + O 2 yielded the largest change in pO 2 (27 mm Hg); this is highly significant relative to baseline or either treatment alone. The effect was positively correlated with baseline pO 2, but 6 of 7 experiments with baseline pO 2 < 10 mm Hg rose above 10 mm Hg after combined treatment. Conclusion: We demonstrated the feasibility of combining hyperglycemia with O 2 to improve tumor oxygenation. However, some cell lines are not susceptible to the Crabtree effect, and the magnitude is dependent on baseline pO 2. Additional or alternative manipulations may be necessary to achieve more uniform improvement in pO 2.

Original languageEnglish (US)
Pages (from-to)494-506
Number of pages13
JournalInternational Journal of Radiation Oncology Biology Physics
Volume51
Issue number2
DOIs
StatePublished - Oct 1 2001

Keywords

  • Crabtree effect
  • Hyperglycemia
  • Hypoxia
  • Oxygen breathing
  • Tumor

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Fingerprint Dive into the research topics of 'Simultaneous administration of glucose and hyperoxic gas achieves greater improvement in tumor oxygenation than hyperoxic gas alone'. Together they form a unique fingerprint.

  • Cite this