Reoxygenation in a C3H mouse mammary carcinoma. The importance of chronic rather than acute hypoxia

Acta Oncol. 1995;34(3):325-8. doi: 10.3109/02841869509093983.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Dioxide / pharmacology
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / radiation effects
  • Female
  • Mammary Neoplasms, Experimental / blood supply
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / physiopathology*
  • Mammary Neoplasms, Experimental / radiotherapy*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred Strains
  • Niacinamide / pharmacology
  • Oxygen / pharmacology
  • Oxygen Consumption / drug effects
  • Oxygen Consumption / radiation effects
  • Radiation-Sensitizing Agents / pharmacology*
  • Radiotherapy Dosage
  • Time Factors

Substances

  • Radiation-Sensitizing Agents
  • Carbon Dioxide
  • Niacinamide
  • carbogen
  • Oxygen