The effect of hydralazine on blood flow and misonidazole toxicity in human tumour xenografts.
The effect of post-irradiation hypoxia induced by 5 or 30 mg/kg hydralazine has been studied in three human tumour xenografts (two rectocolic adenocarcinomas and one melanoma) treated with two doses of misonidazole similar to those used in patients (0.1 and 0.2 mg/g). Only a small sensitization was detected using an in vitro colony assay. These results are in marked contrast to the results obtained with rodent tumours. This difference between human tumour xenografts and rodent tumours might be explained by differences in the reduction of tumour blood flow after hydralazine administration (5 and/or 10 mg/kg). Using the laser Doppler technique, the tumour blood flow reduction was 33% and 25% of the control for NA11 and HRT18 tumours, respectively. In contrast, hydralazine induced a 60-70% reduction in blood flow in the murine SCCVII tumour. Using the fluorescent marker Hoechst 33342, the reduction in perfusion was again more pronounced in the murine tumour as compared to the Na11 and HRT18 xenografts. The differences between human tumour xenografts and rodent tumours are not linked to the mouse strain used (nude versus C3H) nor to a tumour bed effect.
Guichard
M
M
Laboratoire de Radiobiologie Cellulaire (Unité Inserm 247), Institut Gustave-Roussy, Villejuif, France.
Lespinasse
F
F
Trotter
M
M
Durand
R
R
Chaplin
D
D
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000528:radiation effects*; D002460:Cell Line; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology*; D008920:Misonidazole / Q000633:toxicity*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply*; D011836:Radiation Tolerance / Q000187:drug effects*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D014183:Transplantation, Heterologous
D006830:Hydralazine; D008920:Misonidazole