title: The relationship between carbon monoxide breathing, tumour oxygenation and local tumour control in the C3H mammary carcinoma in vivo.
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.
authors.affiliation: Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus.
authors.forename: C
authors.initials: C
authors.lastname: Grau
authors.forename: A A
authors.initials: AA
authors.lastname: Khalil
authors.forename: M
authors.initials: M
authors.lastname: Nordsmark
authors.forename: M R
authors.initials: MR
authors.lastname: Horsman
authors.forename: J
authors.initials: J
authors.lastname: Overgaard
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000494:pharmacology*; D002712:Chlorides; D005260:Female; D000860:Hypoxia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008839:Microelectrodes; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010313:Partial Pressure; D012119:Respiration / Q000187:drug effects / Q000502:physiology; D012413:Rubidium; D012414:Rubidium Radioisotopes
chemical_list: D002712:Chlorides; D012414:Rubidium Radioisotopes; D002248:Carbon Monoxide; D012413:Rubidium; C032710:rubidium chloride; D010100:Oxygen