Hydralazine-induced changes in tissue perfusion and radiation response in a C3H mammary carcinoma and mouse normal tissues.
Hydralazine has been reported to reduce blood perfusion in tumours, thereby increasing hypoxia and subsequently enhancing tumour sensitivity to certain drugs and hyperthermia. We have investigated the ability of hydralazine to induce such changes in a C3H mouse mammary carcinoma and various normal tissues. In tumours, hydralazine (5 mg/kg; i.v.) modified the radiation response, measured by a local tumour control assay, producing an effect equivalent to that seen in tumours made fully hypoxic by clamping. This effect was time-dependent and correlated with the decrease in tissue perfusion estimated by the 86-RbCl extraction procedure. Similar effects were seen in normal skin, although the changes were less dramatic and of a shorter duration. Hydralazine also reduced 86-RbCl uptake in liver, kidney, gut and spleen, but not in bladder, muscle and lung, suggesting that it may have the potential to increase the sensitivity of some normal tissues to hypoxic cell cytotoxins.
Fisker
R V
RV
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus.
Horsman
M R
MR
Overgaard
J
J
D000818:Animals; D015687:Cell Hypoxia; D002712:Chlorides / Q000493:pharmacokinetics*; D005260:Female; D006830:Hydralazine / Q000627:therapeutic use*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000503:physiopathology / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D010477:Perfusion; D011879:Radiotherapy Dosage; D012413:Rubidium / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D002712:Chlorides; D006830:Hydralazine; D012413:Rubidium; C032710:rubidium chloride