title: Tumour radiosensitization by high-oxygen-content gases: influence of the carbon dioxide content of the inspired gas on PO2, microcirculatory function and radiosensitivity.
abstract: OBJECTIVE
  To measure the effects of breathing high-oxygen-content gases, with a CO2 fraction of between 0 and 10%, on tumour radiosensitivity, blood flow and oxygenation.
  
  
  METHODS
  The murine sarcoma F was used, implanted subcutaneously (s.c.) in syngeneic CBA mice. We assessed the induced changes in tumour microregional blood flow and oxygenation using laser Doppler flowmetry, and pO2 histography, respectively. Radiation response was determined using an in vivo-in vitro clonogenic assay 18-20 h post treatment.
  
  
  RESULTS
  The results show that the level of radiosensitization achieved is dependent on both the CO2 content of the inspired gas and the duration of gas breathing. No radiosensitization was evident following inhalation of 90% O2 + 10% CO2. All other gases elicited radiosensitization; however, that achieved with 100% O2 disappeared at the extended preirradiation breathing time of 45 min. At this time, radiosensitization was maintained for gases containing 1%, 2.5%, or 5% CO2. Changes in oxygenation, as measured by PO2 electrodes, did indicate improved oxygenation status during inhalation of the gases. However, the time-course and extent of the changes did not mirror accurately the changes in radiosensitization. All the gases with a CO2 content of 2.5% or greater induced a 10-20% reduction in microregional blood flow, with no change evident following inhalation of 100% O2 or 99% O2 + 1% CO2.
  
  
  CONCLUSIONS
  The data imply that the decreased radiosensitization seen at extended breathing times of oxygen is unrelated to blood flow changes. The fact that radiosensitization is seen with extended breathing times of gases containing 2.5% and 5% CO2, despite blood flow decreases, is indicative of other overriding physiological changes, perhaps related to oxygen utilisation. The studies overall indicate that, at least in the tumour investigated, radiosensitization is not affected if the CO2 content of the inspired gas is reduced from 5% to 2.5%, or even 1%. Further evaluation of the radiosensitizing effects of such gas mixtures is now warranted. In addition, comparison with recent studies of other tumour types, where carbogen has been shown to improve tumour blood flow, suggests that this may be a tumour-specific phenomenon. Based on these data, further effort is required to elucidate the physiological mechanisms that determine these blood flow changes.
authors.affiliation: Gray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, Middlesex, UK. hill@graylab.ac.uk
authors.forename: S A
authors.initials: SA
authors.lastname: Hill
authors.forename: D R
authors.initials: DR
authors.lastname: Collingridge
authors.forename: B
authors.initials: B
authors.lastname: Vojnovic
authors.forename: D J
authors.initials: DJ
authors.lastname: Chaplin
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage*; D015687:Cell Hypoxia; D051379:Mice; D008808:Mice, Inbred CBA; D008833:Microcirculation; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000008:administration & dosage* / Q000097:blood*; D010313:Partial Pressure; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D012513:Sarcoma, Experimental / Q000097:blood / Q000532:radiotherapy*
chemical_list: D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D010100:Oxygen