Further Studies on the Relation Between Radiation Effects, Cell Viability, and Induced Resistance to Malignant Growth

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Abstract
In earlier studies on the effects of x-radiation on the proliferation of tumor particles (primarily of mouse sarcoma 180) grown in vivo and in vitro, it was shown that, while some 60,000 r were required to prevent growth in vitro, 4,000 to 5,000 r were sufficient to prevent growth in vivo (1). Experiments designed to offer some explanation for this difference yielded evidence that the tumor implants which were prevented from proliferating by the smaller dose were attenuated but not entirely destroyed, since animals implanted with the irradiated fragments became resistant, that is “immune,” to further viable grafts of the tumor. Ehrlich, in 1905, originally observed this phenomenon of induced resistance; namely, that viable tumor grafts which fail to grow upon implantation induce resistance in the animal to further tumor grafts. Tumor implants destroyed by heat, formalin, or other means, failed to produce this “immunity.” Utilizing Ehrlich's observations as a test of viability, the author implanted mice with grafts of mouse sarcoma 180 previously irradiated with 60,000 r. These animals did not become resistant to implantation of further viable tumor grafts, thus proving that the dose of radiation required in vitro is actually the destructive dose, not only for the proliferation of the tumor cells, but also for the immunizing agent present in the cell. This work was first carried out on hybrid mice. In further experiments (2), similar results were obtained with a certain inbred strain of rats and a tumor autogenous to the strain (to avoid foreign body reaction); that is, tumor fragments attenuated with a specific dose of irradiation rendered a significant percentage of animals immune. However, with an inbred strain of mice, C57 black, negative results were obtained. The observations set forth above led to further investigations. Experiments were designed to investigate tumors grown in inbred strains of animals, autogenous to the respective strains, regarding: (a) their radiosensitivity and (b) their immunizing properties. Such experiments have a two-fold significance. On one hand, they may help to furnish information regarding threshold doses of radiation for tumors of various types grown in the hosts of origin; on the other hand, they may help to detect the immunizing potentialities of the tumors. Furthermore, there is an advantage in using inbred strains of animals and tumors autogenous to the strain. Since the host and the transplanted tumor are of the same genetic origin, the conditions are similar to those of spontaneous tumors. With the use of transplanted tumors, however, the material secured for experimental purposes is more homogeneous. It is known that spontaneous tumors contain a rather significant amount of fibrous connective tissue and various infiltrating cells; but when they are transplanted from host to host, the resultant tumors consist almost entirely of pure strains of cancer cells.

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