Reoxygenation in a C3H mouse mammary carcinoma. The importance of chronic rather than acute hypoxia.
The role that chronic and acute hypoxia play in tumour reoxygenation after irradiation was investigated in a C3H mouse mammary carcinoma grown in the feet of female CDF1 mice. Tumours at 200 mm3 in size were locally irradiated with a priming dose of 20 Gy and then at various times after given a range of radiation doses under normal or clamped conditions. Local tumour control was determined 90 days later from which the tumour hypoxic fractions were calculated. Untreated tumours contained 23% hypoxic cells. Immediately after 20 Gy this increased to 52% and by 24 h had fallen to 10%. These reoxygenation experiments were repeated, giving either nicotinamide (1000 mg/kg; i.p. injected 30 min before each irradiation) to remove acute hypoxia, or carbogen breathing (for 5 min before and during irradiation) to decrease chronic hypoxia. With nicotinamide the normal hypoxic fraction was reduced to 7%, but after irradiation it had risen to 46% and by 24 h there was full reoxygenation with a value of 5% being observed. Carbogen breathing also decreased the normal hypoxic fraction to 6%, and immediately after irradiation this was increased to 38%. However, by 24 h it was still elevated at around 23%. These results suggest that chronic rather than acute hypoxia is necessary for reoxygenation in this tumour.
Horsman
M R
MR
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus.
Grau
C
C
Overgaard
J
J
D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology* / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D009536:Niacinamide / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011879:Radiotherapy Dosage; D013997:Time Factors
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D010100:Oxygen