EFFECTS OF THE RADIOSENSITISING AGENT NICOTINAMIDE ON RELATIVE TISSUEPERFUSION AND KIDNEY-FUNCTION IN C3H MICE

Nicotinamide is an effective radiosensitiser of murine tumours, functi oning by improving tumour perfusion by decreasing the proportion of in termittently closed capillaries. The effect of nicotinamide on relativ e tissue perfusion of RIF-1 tumour and normal skin, muscle, lung, live r, kidney and spleen were investigated using the Rb-86 extraction tech nique. A dose of 1000 mg/kg was shown to have transient effects on tum our, skin and lung perfusion but to have sustained effects on muscle ( a drop to 80% of control), liver, kidney and spleen (with increases ra nging from 165% to 280% of control) from 0.5 to 4 h after treatment i. e. during the period of maximum radiosensitisation. These increases we re evident at doses as low as 100 mg/kg. The data suggest that the rad iosensitisation induced by nicotinamide in the mouse may be associated with these perfusion changes. Nicotinamide was also shown to have a s ubstantial inhibitory effect on renal function, inhibiting (CrEDTA)-Cr -51 clearance by a factor (+/- 2 SE) of 2.56 +/- 0.19 and I-125-iodohi ppurate clearance by a factor of 2.07 +/- 0.45 at 1000 mg/kg. These ef fects were shown to be dose-related, and to be evident at doses from 4 00 mg/kg upwards. This suggests that nicotinamide potentiation of co-a dministered cytoxic agents may be mediated by reduced renal clearance of the cytotoxic drug, thus increasing the plasma half-life.