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Effect of Changing Tumor Oxygenation on Glycolytic Metabolism in a Murine C3H Mammary Carcinoma Assessed by in Vivo Nuclear Magnetic Resonance Spectroscopy

Lookup NU author(s): Dr Ross Maxwell

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Abstract

The rate of conversion of D-[1-13C]glucose into [3-13C]lactate (apparent glycolytic rate) has been determined in C3H murine mammary carcinomas in vivo using tumor-selective 13C nuclear magnetic resonance spectroscopy with 1H-13C cross-polarization. Under conditions of acute hypoxia induced by breathing carbon monoxide at 660 ppm, the apparent glycolytic rate was 0.0239 6 0.0019 min21. The proportion of 13C label incorporated into [4-13C]glutamate (measured in tumor extracts) was 25-fold lower than that incorporated into [3-13C]lactate, reflecting a very limited oxidative metabolism during this hypoxic episode. For animals breathing air or carbogen (95% O2 1 5% CO2), the calculated glycolytic rates were correspondingly lower (0.0160 6 0.0021 min21 and 0.0050 6 0.0011 min21, respectively). Although 13C labeling of glutamate at C4 was still an order of magnitude lower than that for lactate at C3 (11-fold for air and 9-fold for carbogen), these ratios did show a greater degree of oxidative metabolism than that seen in animals breathing carbon monoxide at 660 ppm. The marked difference in apparent glycolytic rate for this tumor model between well-oxygenated and hypoxic conditions demonstrates a substantial Pasteur effect (inhibition of glycolysis by oxygen). Dynamic 13C nuclear magnetic resonance spectroscopy provides a noninvasive estimate of tumor glycolysis that can be used to evaluate the relationship between oxygenation and energy metabolism, and this has potential consequences for the sensitivity of hypoxic cells to treatment and their ability to promote angiogenesis.


Publication metadata

Author(s): Nielsen FU, Daugaard P, Bentzen L, Stodkilde-Jorgensen H, Overgaard J, Horsman MR, Maxwell RJ

Publication type: Article

Publication status: Published

Journal: Cancer Research

Year: 2001

Volume: 61

Issue: 13

Pages: 5318-5325

ISSN (print): 0008-5472

ISSN (electronic): 1538-7445

Publisher: American Association for Cancer Research

URL: http://cancerres.aacrjournals.org/cgi/reprint/61/13/5318


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