Effect of nitro-L-arginine on blood flow, oxygenation and the activity of hypoxic cell cytotoxins in murine tumours.
This study was an investigation into the ability of nitro-L-arginine to change blood flow, oxygenation status and the activity of hypoxic cell cytotoxic agents in two different transplanted murine tumours. The tumour models were the C3H mammary carcinoma grown in the feet of female CDF1 mice and the SaF grown on the backs of CBA mice. Treatments were carried out in restrained non-anaesthetised animals when tumours were about 100 to 200 mm3 in size. Blood flow was monitored using laser Doppler flowmetry; oxygen partial pressure (pO2) distributions were obtained with an Eppendorf oxygen electrode; and response to treatment with hyperthermia (43.5 degrees C; 30 min) and RB6145 (250 mg kg-1;i.p.) assessed using a tumour growth delay assay. Nitro-L-arginine (10 mg kg-1; i.v.) significantly reduced blood flow by around 40-60% within 15 min after injection in C3H tumour and by 30 min in the SaF. However, nitro-L-arginine had absolutely no effect on tumour pO2 measured at the time of maximal blood flow reduction in both tumour types. It also failed to enhance the response of the C3H tumour to heat, but did produce a small yet significant increase in the response of the SaF tumour to RB6145.
Horsman
M R
MR
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus C. Denmark.
Chaplin
D J
DJ
Hill
S A
SA
Arnold
S
S
Collingridge
D
D
Radacic
M
M
Wood
P J
PJ
Overgaard
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015687:Cell Hypoxia; D005260:Female; D006979:Hyperthermia, Induced; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D019335:Nitroarginine / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects; D012513:Sarcoma, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000628:therapy
D000970:Antineoplastic Agents; D009593:Nitroimidazoles; C067834:RB 6145; D019335:Nitroarginine