We evaluated the sensitizing effect of nicotinamide plus carbogen (N&C) and the relative biological effectiveness (RBE) of pions on microscopic tumors where necrotic tumor centers have not yet been established. Female C3H/He mice and SCCVII tumors were used. The irradiation started two days after tumor implantation. In experiment 1, the tumor beds were irradiated at various doses with 250 KVp photons in 5 fractions over 5 days. Nicotinamide (500 mg/kg/mouse/day in 0.2 ml) was injected intraperitoneally (i.p.) 60 min before irradiation, and carbogen (95% O2 + 5% CO2) was flushed at the rate of 10 l/min for 10 min before irradiation and throughout the entire irradiation procedure. In experiment 2, the tumor beds were irradiated at various doses with pions or 250 KVp photons in 10 fractions over 5 days. In both experiments, the mice were observed for 100 days. The rate of tumor appearance was evaluated and the 50% tumor control dose (TCD50) calculated. The sensitizing ratio (SR) of N&C obtained from the TCD50 assay was 1.46 and the RBE of pions was 1.24. The SR of N&C and the RBE of pions were lower for microscopic tumors than those previously reported for macroscopic tumors. These results were probably due to the absence or reduced presence of radiobiological hypoxic component in the microscopic lesion. However, N&C can be considered to provide an advantage for treatment of even clinical microscopic tumors.

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