The relationship between carbon monoxide breathing, tumour oxygenation and local tumour control in the C3H mammary carcinoma in vivo

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Abstract

The effect of acute carbon monoxide (CO) breathing on blood oxygenation and tumour hypoxia was related to the radiation response of the C3H/Tif mammary carcinoma. Blood gas analysis showed that CO breathing caused a time- and dose-dependent formation of carboxyhaemoglobin (HbCO), a significant left shift of the oxygen dissociation curve and a reduction in tumour blood perfusion. These factors all contributed to a marked drop in tumour oxygen supply. In agreement with this, tumour hypoxia was found to be significantly increased: Microelectrode PO2 measurements showed a clear relationship between CO concentration and the proportion of low PO2 measurements (<or = 5 mmHg). The fraction of clonogenic hypoxic cells increased from 8% in air-breathing animals to 13%, 18% and 54% with 75,220 and 660 p.p.m. CO respectively. The tumour hypoxia resulted in significant radiation modification. The local tumour control after single-dose and fractionated irradiation gave TCD50 enhancement ratios (relative to air-breathing controls) of 0.90, 0.85 and 0.89 for single dose and five or ten fractions given in 5 days (P <0.005 for all values). For 15 fractions in 5 days with 6- 6- and 12 h intervals, the TCD50 was similar in CO- and air-breathing mice, presumably as a consequence of insufficient reoxygenation during the short inter-fraction intervals. It is concluded that elevated HbCO levels to increased tumour hypoxia and that the induced hypoxia has a significant impact on the local tumour control also after fractionated irradiation.
Original languageEnglish
JournalBritish Journal of Cancer
Volume69
Issue1
Pages (from-to)50-7
Number of pages8
ISSN0007-0920
Publication statusPublished - 1 Jan 1994

Keywords

  • Animals
  • Anoxia
  • Carbon Monoxide
  • Chlorides
  • Female
  • Male
  • Mammary Neoplasms, Experimental
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred DBA
  • Microelectrodes
  • Neoplasm Transplantation
  • Oxygen
  • Oxygen Consumption
  • Partial Pressure
  • Respiration
  • Rubidium
  • Rubidium Radioisotopes

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