制癌剤の副作用に関する研究

第1編 骨髄培養による骨髄障害の研究

抄録

Since there is a considerable individual difference in bone-marrow disturbances induced by the administration of anticancer agents, the author conducted a series of study on human bone marrow by the clinical tissue culture method devised by Hiraki et al. for the purpose to know the susceptibility of bone-marrow in the individuals bearing cancer, prior to the administration of anticancer agent. The anticancer agents used were Mitomycin C, Cyclophosphamide and Chromomycin A₃, and these were added to the tissue culture at varying concentrations. Observations were carried out as to their effects on the growth of bone-marrow in order to find out the tolerance to anticancer agents of human bone-marrow in in vitro. The results of these observations were compared with those clinical examinations such as the extent of bone-marrow disturbances brought about by the clinical application of each of these anticancer agents, histological pictures of the bone-marrow prior to the administration of the agent, the number of peripheral leucocytes, the serum protein contents, and ratio A/G before the administration of the agent. The findings of the present study are briefly presented in the following.
1. By conducting tissue culture of the bone-marrow obtained from noncancer bearing and cancer bearing patients with the addition of various anticancer agents in varying concentrations, the in vitro tolerance of the bone-marrow to these agents was studied.
i) In the case of bone-marrow tissue culture with the addition of Mitomycin C, both the bone-marrow of the patients with stomach-cancer and that of non-cancer bearing patients showed a marked individual difference in the tolerance to the anticancer agents, and the maximum tolerance proved to be about six time that of the minimum.
ii) In the tissue culture with the addition of Cyclophosphamide, likewise the bone-marrow of both non-cancer bearing and stomach-cancer bearing patients showed the difference of as much as three-fold between its maximum tolerance and the minimum. This proves that the range of individual differences in the tolerance is narrower than that observed in the case with the addition of Mitomycin C.
iii) In the tissue culture with the addition of Chromomycin A₃ the range of individual differences in the tolerance to it was about two-fold between its maximum and the minimum with the bone-marrow of stomach-cancer bearing patients while it was about three-fold in the case with non-cancer bearing patient. This denotes as in the case with the addition of Cyclophosphamide that the range of the individual differences in the tolerance is narrower than that with Mitomycin C.
2. The range between the maximum tolerance and the minimum observed in the bone-marrow in tissue culture is widest in the addition of Mitomycin C, followed by the range in the case with Cyclophosphamide and Chromomycin A₃. However, the decreasing rate of the peripheral leucocytes in the patients after the administration of the agent in clinic proved to be highest with Mitomycin C, followed by that with Chromomycin A₃ and Cyclophosphamide. This fact reveals an interesting mutual relationship between the tolerance range observed in the bone-marrow tissue culture just described and the decreasing rate of peripheral leucocytes after clinical administration of these agents.
3. There was recognized a close mutual relationship between the degree of tolerance to the anticancer agents in the bone-marrow tissue culture added with these agents and the decreasing rate of peripheral leucocytes in the patients administered with these same agents. This finding indicates that the bone-marrow tissue culture conducted with anticancer agent prior to its use can predict the tolerance of the bone-marrow to the agent.