THE RADIATION RESPONSE OF KHT SARCOMAS FOLLOWING NICOTINAMIDE TREATMENT AND CARBOGEN BREATHING

Preclinical investigations have demonstrated that both diffusion- and perfusion-limited hypoxic cells may exist in tumors. One approach to t arget such hypoxic cell subpopulations is through the combined applica tion of nicotinamide (NIC) administration and carbogen (5% CO2:95% O-2 ) breathing. Because carbogen pre-irradiation breathing time (PIBT) ca n markedly influence the radiosensitizing effectiveness of this gas mi xture, in the present experiments the effect of localized radiation on the transplantable KHT sarcoma was investigated in mice receiving NIC while breathing carbogen for various periods of time. When mice were given carbogen prior to radiation therapy, there was a minimum in tumo r cell survival for PIBTs of 2-30 min. Longer PIBTs led to a loss of t he radiosensitizing effect. NIC, administered as a 1000-mg/kg dose, ef fectively enhanced radiation cell killing in this tumor if given 45 mi n to 2 h prior to radiotherapy. In experiments in which either agent w as combined on its own under optimum conditions (carbogen, 10 min PIBT ; or NIC, 1000 mg/kg 2 h prior to irradiation), with a range of single doses of radiation, the results showed an enhancement ratio of simila r to 1.9 as determined from the ratio of the slopes of the cell surviv al curves obtained in the absence or presence of the radiation sensiti zer. This sensitizing effect could not be increased further when NIC a nd carbogen breathing were combined under optimum conditions.