Action of Bacterial Toxins on Tumors. II. Effect of Sulfanilamide on Toxin-Induced Hemorrhage

It has been pointed out 1 that the lethal action of Salmonella endotoxin is markedly reduced in vivo by the administration of various sulfanilamide compounds. This lethal factor parallels in action the hemorrhagic factor present in the endotoxins of most gram-negative bacteria. 2 The parallelism of action in respect to sulfanilamide, as indicated by the following experiments, suggests the possibility that the two factors are similar, if not identical.

The toxic material used in this study was made by growing Salmonella typhimurium in a synthetic liquid medium. The methods for extraction have been previously described. 1 A single uniform batch of antigenic material representing the growth from forty liters of medium was used in both this and the previous study. 1 Observations of hemorrhagic effect were made on 7-day-old implanted tumors (Mouse Sarcoma 180).

Rockland mice bearing tumors were given 20 mg of neutralized sulfanilamide by stomach tube, followed by the intraperitoneal administration of the toxin in aqueous solution. Six to 10 hr after treatment the tumors were examined for hemorrhage.

From the table it is seen that the minimum hemorrhage dose is about 6.5 μg of dry weight of toxic material.∗ The minimum hemorrhage dose (M.H.D.) is defined as the smallest quantity of antigen which, when injected intraperitoneally, causes from slight (+) to marked (+++) hemorrhage in the tumors of 50% of the tested animals.

The minimum lethal dose of the endotoxin preparation used in this and the previous study 1 was approximately 1.3 mg for non-tumor-bearing mice. When this amount of the material was injected into tumor-bearing mice protected against death by adequate sulfanilamide treatment, marked hemorrhage occurred in the tumor, indicating that sulfanilamide does not negate the hemorrhage factor of the antigen at this dosage of the antigen.