BW12C-induced changes in haemoglobin-oxygen affinity in mice and its influence on the radiation response of a C3H mouse mammary carcinoma.
The effect of the substituted benzaldehyde BW12C on haemoglobin-oxygen binding affinity, tumour radiation response and blood perfusion were investigated in a C3H mouse mammary carcinoma grown in the feet of CDF1 mice. Mouse P50 (partial pressure of oxygen at half saturation) was estimated using an ABL blood gas analyzer; radiation response determined from tumour regrowth and local tumour control assays; and tumour blood perfusion measured with a 86RbCl extraction procedure. A single intravenous injection of BW12C substantially decreased mouse P50. This effect was dependent on the time after injection with the nadir observed within 15 min and only returning to normal after several hours. It was also dependent on drug dose, the decrease becoming larger with increasing concentration, reaching a maximum 50% reduction at 70 mg/kg. The decrease in P50 could be maintained for at least 6 h following injection of 70 mg/kg, if mice were also given 25 mg/kg at hourly intervals. However, no changes in radiation response or tumour blood perfusion were observed with either single or multiple administrations of BW12C. These results suggest that BW12C induced changes in tumour hypoxia reported by several groups of workers, may not be entirely the result of a change in haemoglobin-oxygen affinity.
Horsman
M R
MR
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus.
Overgaard
J
J
D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000532:radiotherapy*; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000097:blood; D010108:Oxyhemoglobins / Q000187:drug effects*; D010313:Partial Pressure; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013997:Time Factors
D001547:Benzaldehydes; D010108:Oxyhemoglobins; D011837:Radiation-Protective Agents; C039599:5-(2-formyl-3-hydroxyphenoxy)pentanoic acid; D010100:Oxygen