SENSITIZATION TO X-RAYS BY SODIUM ARSENITE OR HEAT IN NORMAL-CELLS AND IN CELLS WITH AN INDUCED TOLERANCE FOR HEAT AND ARSENITE

In this study we compared sensitization to x-rays by heat or sodium ar senite and the effect of an induced heat or arsenite resistance on rad iosensitization, Treatment of Reuber H35 hepatoma cells with either he at or arsenite causes a dose-dependent radiosensitization. Based on a comparison of isosurvival doses for arsenite and heat, arsenite causes a stronger enhancement of the radiosensitivity. Radiosensitization in creases exponentially with increasing sensitizer dose. It is gradually lost when the time interval between irradiation and treatment with he at or arsenite increases, depending on the treatment sequence. For x-r ays prior to heat, radiosensitization disappears approximately twice a s fast as in the reverse case. Arsenite radiosensitization shows appro ximately the same kinetics for an isoeffective combination, but slight ly longer times are needed for the complete clearance of the interacti on. As with heat, an exposure to arsenite induces a stress response in cultured cells which results in the development of an increased toler ance towards a second exposure. Heat and arsenite induce self- as well as cross-tolerance. The reduction in arsenite or heat toxicity in tol erant cells is correlated with a reduction in radiosensitization. The mechanisms for heat and arsenite cytotoxicity appear to be different. A combination of non-toxic doses of hear and arsenite has a synergisti c effect on the cytotoxicity. One hour incubation with 0.02 mM arsenit e at 41 degrees C has the same cytotoxicity as 0.2 mM after 3 h incuba tion at 37 degrees C, and the amount of radiosensitization induced by these treatments is approximately the same.