制癌剤の副作用に関する研究

第2編 少量の制癌剤投与による実験腫瘍発育促進に関する細胞学的研究

抄録

In the bone-marrow tissue culture conducted previously the auther found that on the addition of anticancer agents in a very low concentration the agent rather accelerated the growth of the human bone-marrow cells obtained from the cancer bearing and noncancer bearing individuals. Therefore, it has been assumed that the administration of a small amount of anticancer agent might accelerate the cancer growth rather than inhibit it. On the basis of this supposition, a series of experiments were conducted to see the effects of various anticancer agents on cancer bearing mice as well as on tumor growth itself.
For this purpose three strains of mouse ascites tumor cells, namely, Ehrlich ascites tumor cells, lymphoid leukemic cells strain SN 36, and Sarcoma 180 cells were selected and these were inoculated intraperitoneally into mice.
Next, anticancer agents, namely, Mitomycin C, Cyclophosphamide, and Chromomycin A₃, each in the concentration of 1/20 and 1/40 of their effective dose, were administered to these mice receiving transplantation of tumor cells, at two different stages, one at an early stage after the transplantation of cancer cells (initial stage) and the stage where the animals were on the threshold of death from tumor (terminal stage). The results of observations are briefly presented in the following.
1. Looking over the survival curves and the average of survival time of the cancer bearing mice, in the group of animals that received the anticancer agent at the initial stage of cancer there could be observed no definite trend but there seemed to be a strong tendency to prolong the average of survival time. In contrast to this group, those received anticancer agent at the terminal stage definitely showed the shortening of the average of survival time.
2. As for the changes in the increase of body weight and the total packed cell volume, while the group receiving the administration of anticancer agent at the initial stage generally showed lower values than the control group, and the group receiving it at the terminal stage showed higher values, indicating the acceleration of tumor growth.
3. With respect to the mitotic index, in the group receiving the administration at the initial stage the index fell on the whole, but it recovered markedly after lapse of 72 hours. In the group receiving the administration at the terminal stage there could be observed two different groups; one that had a decreasing tendency in the index value after the administration but it turned to rise markedly after 72 hours, and the other group that showed a marked rise in the index value immediately after the administration and maintaining this high level even after the lapse 72 hours.
4. As for the rate of DNA synthesis in tumor cells (computed on the basis of the labeling index with the combined use of ³H-thymidine and autoradiography), the rate as a whole tended to fall in the group receiving the administration of anticancer agent at the initial stage, whereas in the group receiving it at the terminal stage it tended to increase.
5. By the same technique with the use of ³H-thymidine the average of grain count in labeled tumor cells was calculated to see the change if any. As the result it was found that on the whole the group receiving the anticancer agent at the initial stage tended to show a fall in the average of grain count, while the group receiving it at the terminal stage revealed a rise in the average of grain count, suggesting that the rate of DNA synthesis was decreased in the former group while it was accelerated in the later.