Direct evidence that hydralazine can induce hypoxia in both transplanted and spontaneous murine tumours.
Hydralazine can substantially decrease blood flow and increase hypoxia in transplanted tumours. Previous indirect studies have suggested that hydralazine does not induce such effects in spontaneous tumours. We have now directly investigated the ability of hydralazine to increase hypoxia in both transplanted and spontaneous murine tumours by measuring tumour oxygen partial pressure (pO2) distributions using an Eppendorf oxygen electrode. Spontaneous tumours arose at different sites in CDF1 mice, while transplanted tumours were produced by implanting a C3H mouse mammary carcinoma on the backs of the same mouse strain. Measurements of pO2 were made in anaesthetised mice immediately before and 45 min after an intravenous injection of 5 mg kg-1 hydralazine. In the transplanted tumours hydralazine significantly decreased tumour oxygenation, such that the percentage of pO2 values < or = 5 mmHg increased from 45% to 87%, and median pO2 decreased from 5 to 3 mmHg. Similar significant changes were induced by hydralazine in the spontaneous tumours, the percentage of pO2 values < or = 5 mmHg increasing from 60% to 94% while the median pO2 values decreased from 8 to 2 mmHg. These results clearly show that there is no difference in the response of transplanted and spontaneous mouse tumours to hydralazine.
Horsman
M R
MR
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus, Denmark.
Nordsmark
M
M
Høyer
M
M
Overgaard
J
J
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D004566:Electrodes; D005260:Female; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000032:analysis / Q000378:metabolism*; D010313:Partial Pressure
D006830:Hydralazine; D010100:Oxygen