Mixed bacterial toxins in the treatment of tumors. III. Effect of tumor removal on the toxicity and mortality rates in mice.

that bacterial toxins from Serr&ia rnarc&wena and Streptococcus pyogenes are considerably less toxic when adminis tered to normal mice than when given to mice bearing Sarcoma 37 (1, @). A @0-to SO-fold dosage increase of the toxins is required to produce tissue changes and mortality rates in normal mice equiv alent to those produced in tumor-bearing animals. This difference in susceptibility could be caused either by the toxins' primary effect on the tumor, resulting in cellular breakdown and toxicity to the host, or by the depletion of some resistance factor by the presence of the tumor. These alternatives could be tested by removing the tumor when it has reached the appropriate size and age for ther apy. If the tumor-excised mice react to the toxins as do normal mice, the increased sensitivity of the tumor-bearers is not due to an irreversibly altered host but is a result of the reaction of toxin with tumor. If, on the other hand, the mice after tumor removal continue to show mortality rates corn parable to those of the tumor-bearing animals, the host has been altered by the tumor in such a way as to increase his susceptibility to the toxins. The following experiments were designed to determine whether the host's resistance to toxin could be restored by the surgical removal of the tumor. In the first experiment (Exp. I) 2@0 male Swiss ICR mice,7 weeksold, weighingbetween @8 and 33 gm., were given injections subcutaneously in the interscapular region of approximately 5@mil lion cells of ascites Sarcoma 37. In addition, 48 mice of the same age and weight were set aside as normal controls. After 6 days all mice were weighed again, the tumors measured, and those mice having well defined tumors measuring be tween 1.5 and @.5 sq. cm. at the base were selected for the experiment. The tumor-bearing mice were divided into Group A, with 65 mice, and Group B, with 1@1 mice. The dorsally located tumors, together with their overlying skin, were-resected by an elliptical incision from the 65 mice of Group A under nern butal anesthesia, and the skin was closed with sur gical clips. Care was taken to leave no obvious residual tumor. The whole operative procedure was completed in @†" 4 minutes per mouse, and the excised tumors were preserved for histopathologi cal study. The next day the mice in both Groups A and B, and the …