title: Relationship between tumour oxygenation, bioenergetic status and radiobiological hypoxia in an experimental model.
abstract: 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.
authors.affiliation: Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus.
authors.forename: M
authors.initials: M
authors.lastname: Nordsmark
authors.forename: C
authors.initials: C
authors.lastname: Grau
authors.forename: M R
authors.initials: MR
authors.lastname: Horsman
authors.forename: H S
authors.initials: HS
authors.lastname: Jörgensen
authors.forename: J
authors.initials: J
authors.lastname: Overgaard
mesh_terms: 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
chemical_list: D010710:Phosphates; D011838:Radiation-Sensitizing Agents; D012265:Ribonucleotides; D002245:Carbon Dioxide; D010758:Phosphorus; C011700:carbogen; D010100:Oxygen