Experimental basis of combination therapy of X-ray and bleomycin

When mice bearing Ehrlich ascites tumor cells in the plateau phase received a single shot of x-ray or Bleomycin, the surviving fraction of tumor cells, as determined by agar colony assay, increased with time after administration. This was attributed to repair after the potentially lethal damage given by each agent. When both x-ray and Belomycin were administered to the mice simultaneously, survival of tumor cells assayed as a function of time was found to be slightly but consistently below the level which was expected from the additional effect of each agent. The observed pontentiating effect disappeared if two agents were given at intervals of more than 3 hours irrespective of the order of administration. These findings suggest that (1) a portion of the damages, either potentially lethal or non-lethal, induced by both agents associated or interacted mutually and was converted to the lethal damage; (2) the capability of damage to associate was rapidly diminished. From the experimental point of view, it can be concluded that simultaneous use is more effective for tumor cell sterilization than other schedules in combination of x-ray and Bleomycin. (J.P.N.)