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Factors Controlling Oxygen Utilization

  • John Biaglow
  • Mark Dewhirst
  • Dennis Leeper
  • Randy Burd
  • Steve Tuttle
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 566)

Abstract

We demonstrate, theoretically, that oxygen diffusion distance is related to the metabolic rate of tumors (QO2) as well as the oxygen tension. The difference in QO2 rate between tumors can vary by as much as 80-fold. Inhibition of oxygen utilization by glucose or chemical inhibitors can improve the diffusion distance. Combining respiratory inhibitors with increased availability of oxygen will further improve the oxygen diffusion distance for all tumors. A simple means for inhibiting oxygen consumption is the use of glucose (the Crabtree effect). The inhibition of tumor oxygen utilization by glucose occurs in R323OAc mammary carcinoma and 9L glioma cells. However, stimulation of oxygen consumption is observed with glucose in the Q7 hepatoma cell line. MIBG, a known inhibitor of oxygen utilization, blocks oxygen consumption in 9L, but is weakly inhibitory with the Q7. Q7 tumor cells demonstrate an anomalous behavior of glucose and MIBG on oxygen consumption. Our results clearly demonstrate the necessity for comparing effects of different agents on different tumor cells. Generalizations cannot be made with respect to the choice of inhibitor for in vivo use. Our work shows that oxygen consumption also can be inhibited with malonate and chlorosuccinate. These substrates may be effective in vivo, where glucose is low and glutamine is the major substrate. Our results indicate that information about individual tumor substrate-linked metabolic controls may be necessary before attempting to inhibit oxygen utilization in vivo for therapeutic benefit.

Keywords

Oxygen Consumption Diffusion Distance Krebs Cycle Radiation Response Oxygen Utilization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • John Biaglow
  • Mark Dewhirst
  • Dennis Leeper
  • Randy Burd
  • Steve Tuttle

There are no affiliations available

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