Abstract
1) First of all I must take the question of whether the transplantation of Yoshida sarcoma is caused by the tumor cell itself.
In the experiments with ascites free from cells, only one case out of 15 presents the positive result. Even a single case resulting in a success puts before us a question to be discussed-a question of whether there exists a certain extracellular oncogenic agent such as a virus in this tumor.
Supposing such an agent exists in this tumor, the fluid containing the more of it must present the higher transplantability. As a matter of fact, the tumor ascites diluted 4-17 times, in which a great deal of such an agent, if it exists, might presumably have been contained, bore the negative result with one exception in 15 cases, when tumor cells had been excluded from it; while, the tumor ascites diluted to such a high degree as 5 million times produced the positive result, when a very few tumor cells, even a single one, had been included in it.
If such an agent really exists, moreover, the transplantability of this tumor can not be influenced by the number of the tumor cells, but, in fact, it markedly goes down according to the gradual decrease of the number of tumor cells.
From these facts, it is hardly to be believed that there exists any such extracellular oncogenic agent at all.
Besides, tumor cells were occasionally found in a droplet taken from the supernatant by the centrifugation for 60 minutes at 3, 000 cycles. Although such a cell-containing droplet was omitted, absolute prevention from an entrance, among numerous droplets, might not always be expected. If once this droplet containing cells was inoculated into the peritoneal cavity, it would be an easy task for the cell to proliferate immediately, since 1 or 2 cell inoculation caused the positive result.
Furthermore, from the microscopic findings, the proliferation of tumor cells implanted was seen every time, while the picture of malignant transformation of normal cells in the peritoneal cavity could never be observed.
The course of the disease in the one positive case mentioned above (i. e. positive case in cell-free inoculation) was quite analogous to that of 1 or 2 cell inoculation.
I came thus to the conclusion that the transplantation of Yoshida sarcoma does not depend upon any extracellular oncogenic agent, but upon the proliferation of the implanted tumor cell itself.
2) Next I want to express my opinion on the minimal number of tumor cells necessary for the transplantation of Yoshida sarcoma. Table 10 is compiled, from the results of the transplantation with a small number of tumor cells. Although a successful transplantation could be expected even from one single tumor cell, the positive result was not attained in every case where less than 10 tumor cells were applied and even 23 or 30 cells produced the negative result.
These seem to be due to the following conceivable factors: not all cells used for inoculation were viable or capable of proliferation, one single cell sucked into the micropipette might happen to be a normal cell (monocyte or lymphocyte) occurring among tumor cells; furthermore, the cells once sucked into the micropipette might possibly remain there, failing to reach the peritoneal cavity of a rat, or they might be injured during the process of manipulation and fall into degeneration, though they reach the peritoneal cavity.
In this connection, it was remarkable that successful inoculations were made with such a very small number as 1, 2 or 11 of cells, when the tumor ascites was diluted with physiologic NaCl solution with peritoneal fluid of normal rats as an addition. In other words, it may be supposed that the solution added with peritoneal fluid would work less injury to the cells than plain Tyrode solution or physiologic NaCl solution.These results correspond with the report of Furth and Kahn that with Tyrode solution solely,