Relationship between tumour oxygenation, bioenergetic status and radiobiological hypoxia in an experimental model.
Tumour oxygenation and bioenergetic status were measured in the same tumour and these results related to radiobiological hypoxia. A C3H mouse mammary carcinoma grown in the feet of CDF1 mice was used. Bioenergetic status was assessed by 31P MRS using a SISCO 7 Tesla magnet, oxygen measurements were done by a polarographic electrode and the hypoxic fraction was determined from direct analysis of the radiation dose-response data. During all examinations restrained, non-anaesthetized mice were allowed to breathe either 100% oxygen, carbogen, normal air, carbon monoxide (CO) at 75, 220, or 660 ppm or had blood flow occluded by clamping. Results showed a significant correlation between the radiobiological hypoxic fraction and % pO2 < or = 5 mmHg under the different treatment conditions, whereas no correlation was found between beta nucleosidetriphosphate/inorganic phosphate (beta-NTP/Pi) ratio and either the hypoxic fraction or the % of pO2 values < or = 5 mmHg under the different treatment conditions. In conclusion, oxygen electrode measurements were sensitive to changes in tumour hypoxia whereas the bioenergetic status alone seemed to be a less precise measure of hypoxia in this tumour model. Furthermore, the present study demonstrated that tumour cells in vivo can actually maintain the bioenergetic status during a period of severe hypoxia.
Nordsmark
M
M
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus.
Grau
C
C
Horsman
M R
MR
Jörgensen
H S
HS
Overgaard
J
J
D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D015687:Cell Hypoxia; D004734:Energy Metabolism / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D010100:Oxygen / Q000032:analysis / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010313:Partial Pressure; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus; D011048:Polarography; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012265:Ribonucleotides / Q000378:metabolism
D010710:Phosphates; D011838:Radiation-Sensitizing Agents; D012265:Ribonucleotides; D002245:Carbon Dioxide; D010758:Phosphorus; C011700:carbogen; D010100:Oxygen