Nicotinamide reduces tumour interstitial fluid pressure in a dose- and time-dependent manner.
Nicotinamide radiosensitizes a number of experimental tumours, and increases blood flow and mean pO2 in some tumours. It has been suggested 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, transient vessel non-perfusion, and radiosensitivity after nicotinamide administration were examined in the murine carcinoma NT. Nicotinamide at doses of 500 and 1000 mg kg-1 significantly reduced tumour IFP within 20 min of administration, with recovery to control values by 60-80 min; 100 mg kg-1 had no effect. The percentage of previously non-perfused 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 after nicotinamide administration, this differential effect was abolished. The correlation in the time courses of reduced IFP and increased vessel perfusion after nicotinamide administration suggest that decreased IFP may accompany vessel reperfusion. However, 1000 mg kg-1 of nicotinamide radiosensitized the NT carcinoma 80 min after administration, whilst no radiosensitization was seen within 10 min. Thus it is unlikely that increased vessel perfusion is the sole mechanism of nicotinamide-induced radiosensitization in this tumour.
Peters
C E
CE
Gray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, Middlesex, UK.
Chaplin
D J
DJ
Hirst
D G
DG
D000230:Adenocarcinoma / Q000098:blood supply / Q000628:therapy*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects*; D005260:Female; D051379:Mice; D008808:Mice, Inbred CBA; D009536:Niacinamide / Q000494:pharmacology*; D011312:Pressure; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013997:Time Factors
D011838:Radiation-Sensitizing Agents; D009536:Niacinamide