EFFECT OF NITRO-L-ARGININE ON BLOOD-FLOW, OXYGENATION AND THE ACTIVITY OF HYPOXIC CELL CYTOTOXINS IN MURINE TUMORS

This study was an investigation into the ability of nitro-L-arginine t o change blood flow, oxygenation status and the activity of hypoxic ce ll cytotoxic agents in two different transplanted murine tumours. The tumour models were the C3H mammary carcinoma grown in the feet of fema le CDF1 mice and the SaF grown on the backs of CBA mice. Treatments we re carried out in restrained non-anaesthetised animals when tumours we re about 100 to 200 mm(3) in size. Blood flow was monitored using lase r Doppler flowmetry; oxygen partial pressure (pO(2)) distributions wer e obtained with an Eppendorf oxygen electrode; and response to treatme nt 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 the C3H tumour and by 30 min in the SaF. However, nitro-L-arginine had absolutely no effect on tumour pO(2 ) 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 hea t, but did produce a small yet significant increase in the response of the SaF tumour to RB6145.