Radiosensitization of SCCVII tumours and normal tissues by nicotinamide and carbogen: analysis by micronucleus assay

The radiosensitizing effect on SCCVII tumours of carbogen (95% O2 + 5% CO2) combined with nicotinamide was investigated using the micronucleus assay and an in vivo/in vitro colony formation assay following single irradiation. The effects on intestinal crypt cells and bone marrow cells were also examined in mice. The frequency of micronuclei in tumours increased with an increase in the nicotinamide dose (administered 1 h before the irradiation of 5 Gy) from 0.1 to 1.0 mg/g, and showed a 1.3-fold increase at 1.0 mg/g when compared with radiation alone. The micronucleus frequency showed a more marked increase following irradiation combined with nicotinamide and carbogen inhalation starting 15 min before irradiation. The radiosensitizing effect reached a plateau at a nicotinamide dose of 0.1 mg/g in combination with carbogen, giving an enhancement ratio (ER) of 1.8 relative to radiation alone at 2 Gy. In the radiation dose range of 5-20 Gy, ERs of 1.8-1.9 and 1.5 (at a 10% cell-survival level) were obtained for the combination of 0.1 or 1.0 mg/g nicotinamide and carbogen and for carbogen alone, respectively. A slight increase in the regeneration response of the jejunum and the bone marrow was observed following irradiation combined with 0.1 mg/g nicotinamide and carbogen, yielding ERs of 1.07 for the jejunum and 1.15 for the bone marrow. Thus, the nicotinamide/carbogen combination, with its large therapeutic gain factor at low doses and proven low toxicity in humans, seems to improve the response of cancer to radiotherapy.