title: Effect of vascular marker Hoechst 33342 on tumour perfusion and cardiovascular function in the mouse.
abstract: The fluorescent stain Hoechst 33342 (H33342) has been employed extensively as an in vivo marker of functional tumour vasculature. We have found that H33342 causes a transient, dose-dependent decrease in tumour red blood cell (RBC) flow in SCCVII tumours as measured using laser Doppler flowmetry. After intravenous bolus injection of 15 mg kg-1 to anaesthetised mice, blood flow in subcutaneous back tumours declined to 19 +/- 11% of pretreatment values, returning to normal in less than 7 min. The effect was less pronounced in mice bearing foot tumours in which flow decreased to 52 +/- 14% of pretreatment values in unanaesthetised mice and to 50 +/- 15% in anaesthetised animals. RBC flow in foot tumours remained significantly depressed for only 2-3 min. A dose of 5 mg kg-1 was not significantly vasoactive in back tumours. H33342 also caused a transient 20 +/- 6 mmHg decline in mouse arterial blood pressure. Blood pH and haematocrit, and tumour cell oxygen consumption were unchanged by H33342. H33342-induced flow changes did not affect results obtained using an in vivo double staining protocol provided that the interval between stain injections was greater than 5 min. Due to its transient effects on tumour perfusion, the stain caused radiobiological tumour hypoxia if injected immediately prior to X-irradiation. Injection 20 min before irradiation had no influence on tumour radiation response. We conclude that the transient nature of H33342-induced perturbations in mouse cardiovascular physiology and tumour blood flow must always be considered but do not preclude the use of the stain as a vascular marker to detect spontaneous tumour blood flow fluctuations or acute hypoxia.
authors: Medical Biophysics Unit, BC Cancer Research Centre, Vancouver, Canada.
authors: M J
authors: MJ
authors: Trotter
authors: P L
authors: PL
authors: Olive
authors: D J
authors: DJ
authors: Chaplin
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D005456:Fluorescent Dyes / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000532:radiotherapy; D010101:Oxygen Consumption / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D001562:Benzimidazoles; D005456:Fluorescent Dyes; C017807:bisbenzimide ethoxide trihydrochloride