POSSIBLE MECHANISMS INVOLVED IN TUMOR RADIOSENSITIZATION FOLLOWING NICOTINAMIDE ADMINISTRATION

Despite continued interest in the administration of nicotinamide (NA) as a tumor-specific radiosensitizer (an effect thought to be related t o increases in tumor blood flow and oxygenation), little is known abou t the underlying mechanism(s) of this effect. The aim of this study wa s to investigate metabolic changes following NA application in both tu mor and normal tissues. Increased concentrations of NAD(+) were measur ed in DS-sarcomas, liver, and kidney tissue, with no changes in concen trations in resting skeletal muscle. Further investigations also exami ned the concentrations of glucose, lactate, ATP, ADP and AMP in tumor and resting skeletal muscle tissue following NA application. Here, the only change detected was an increase in lactate levels in tumor tissu e. The changes in NAD(+) concentrations described correlate well with reported changes in tissue blood flow measured following NA. On the ba sis of changes in tumor blood flow, oxygenation and metabolite concent rations found in this and other recent studies, possible mechanisms fo r tumor radiosensitization following nicotinamide administration are c onsidered.