NICOTINAMIDE REDUCES TUMOR INTERSTITIAL FLUID PRESSURE IN A DOSE-DEPENDENT AND TIME-DEPENDENT MANNER

Nicotinamide radiosensitizes a number of experimental tumours, and inc reases blood flow and mean pO(2) in some tumours. It has been suggeste d that nicotinamide reduces tumour interstitial fluid pressure (IFP), thereby reducing transient vessel non-perfusion and acute hypoxia, and radiosensitizing tumours. To test this hypothesis, tumour IFP, transi ent vessel non-perfusion, and radiosensitivity after nicotinamide admi nistration were examined in the murine carcinoma NT. Nicotinamide at d oses of 500 and 1000 mg kg(-1) significantly reduced tumour IFP within 20 min of administration, with recovery to control values by 60-80 mi n: 100 mg kg(-1) had no effect. The percentage of previously non-perfu sed vessels that became perfused 20 min after administering 1000 mg kg (-1) of nicotinamide significantly exceeded the percentage that became perfused within 20 min in the absence of nicotinamide. By 90 min afte r nicotinamide administration, this differential effect was abolished. The correlation in the time courses of reduced IFP and increased vess el perfusion after nicotinamide administration suggest that decreased IFP may accompany vessel reperfusion. However, 1000 mg kg(-1) of nicot inamide radiosensitized the NT carcinoma 80 min after administration, whilst no radiosensitization was seen within 10 min. Thus it is unlike ly that increased vessel perfusion is the sole mechanism of nicotinami de-induced radiosensitization in this tumour.