INFLUENCE OF COMBINED USE OF NICOTINAMIDE AND CARBOGEN ON RAT SPINAL-CORD RADIATION TOLERANCE

The effect of combining oxygen or carbogen breathing with the systemic administration of nicotinamide (NA) on spinal cord tolerance in Ethrane anesthetised male WAG/Rij rats has been investigated. Ten fraction experiments were carried out with dairy (24 h between fractions) and twice a day fractionation (8 h between fractions). Nicotinamide (500 mg/kg) was injected 1 h prior to each irradiation. In addition, a 10-fraction experiment with daily intervals was carried out in which NA was added immediately after irradiation under carbogen breathing conditions. Single dose irradiations showed a minimal decrease in ED(50) from 21 Gy in oxygen conditions to 19.9 Gy in carbogen conditions and 19.4 Gy when combined with NA. In the fractionation experiments, comparing the response to irradiation in oxygen (O) and nicotinamide oxygen (NO) conditions for the 24-h interval experiment, the ED(50) for O was 61.6 Gy compared with 54.5 Gy for NO. When carbogen (C) was compared with nicotinamide carbogen (NC), the ED(50) for C was 62.3 Gy and 53.9 Gy for NC. When NA was administered immediately after irradiation under carbogen breathing conditions the ED(50) increased to 57.8 Gy. For twice a day fractionation the modifying effect of nicotinamide was similar to that observed for daily fractionation (ED(50) of 57.9 Gy for O, 57 Gy for C and 50.9 Gy for CN), when corrected for incomplete repair in between the two fractions given on 1 day. In conclusion, combining nicotinamide with irradiation while breathing oxygen or carbogen could lead to a reduction of the spinal cord tolerance of approximately 15%, or even 25% when corrected for biological effectiveness based on the LQ formula. This effect should be taken into account in planning clinical studies.