FURTHER EVALUATION OF NICOTINAMIDE AND CARBOGEN AS A STRATEGY TO REOXYGENATE HYPOXIC CELLS IN-VIVO - IMPORTANCE OF NICOTINAMIDE DOSE AND PREIRRADATION BREATHING TIME

The combination of nicotinamide and carbogen breathing is awaiting cli nical evaluation as a strategy to overcome tumour hypoxia and thus enh ance radiation response. We have continued our evaluation of this appr oach in the murine SCCVII tumour with the aim of determining the impor tance of nicotinamide dose and the pre-irradiation breathing time (PIB T) for carbogen. For carbogen breathing alone maximal enhancement of r adiation response was observed with PIBT's of between 5 and 30 min. Wh en nicotinamide (1,000 mg kg-1 IP) was administered 60 min prior to ir radiation little or no variation in radiation response was observed fo r all the PIBT's examined (5-90 min). Indeed at all PIBT's the cell su rvival obtained for the carbogen nicotinamide and radiation combinatio n was indistinguishable from that expected for a fully aerobic respons e. For PIBT's of 15 and 60 min we examined the influence of nicotinami de doses between 50 and 1,000 mg kg-1. Significant radiosensitising ef fects were observed for all nicotinamide doses tested above 50 mg kg-1 . Moreover for doses of 250 mg kg-1 and above the cell survival data w as consistent with that expected for a fully aerobic response. No addi tional benefit accrued from raising the nicotinamide dose above 250 mg kg-1. These results indicate that significant radiosensitisation may be expected even with clinically achievable nicotinamide doses when it is combined with carbogen breathing. Furthermore, the use of nicotina mide may reduce the critical importance of PIBT on the radiosensitisat ion observed with carbogen.