Reaction of Spontaneous Mouse Carcinomas to Blood-Carried Bacterial Toxins

Abstract

We reported 1 a study on the vascular reactions of a series of growths ranging from benign embryomas and granulomas to very malignant transplantable carcinomas and sarcomas of mice and rats to a blood-carried B. coli toxin of low potency. The phenomenon of the tumor reactivity to bacterial toxin was first described by Gratia and Linz, 2 and confirmed by Shwartzman and Michalowsky. 3 The reaction shows the general characteristics of the Shwartzman phenomenon. Apitz 4 has further proved that still other factors capable of inducing the latter phenomenon in rabbits also induce the phenomenon of the tumor reactivity.

From our investigations we concluded that only those growths showing at the same time malignancy and rapidity of growth present the phenomenon of Gratia and Linz.

As a corollary to this principle it was found on further analysis that the degree of pre-existing necrosis is, generally speaking, a good index of the degree of tumor susceptibility. Necrosis is the expression of a special state of vascular fragility which renders the rapidly growing tumor vulnerable to the injected toxin, even if the latter is practically harmless for the normal animal. Apitz 3 had already noticed a definite relation existing between the microscopic areas of necrosis and the incidence of hemorrhages.

The tumors most susceptible to the B. coli toxin were the fast-growing malignant transplantable tumors of rats and mice. As a result of the phenomenon a good many tumors regressed partially or totally. Regression was also observed after an apparently negative reaction in the tumor. On the other hand, the slower growing malignant spontaneous carcinomas of mice were found practically non-susceptible and their further course was not modified at all.

It is obvious that the phenomenon is conditioned by 2 sets of factors: the intrinsic factor depending on the sensitivity of the tumor itself, and the extrinsic one, depending on the activity, quantity, and route of inoculation of the toxin.