For the purpose of obtaining some knowledge on the participation of host factors in tumor chemotherapy, studies were designed using original Yoshida sarcoma (YS), which is sensitive to cyclophosphamide (CPM), and a CPM-resistant form of YS (YS-R) established by T. KOKAWA in our department.
1) Effect of CPM on YS- and YS-R-bearing rats: Donryu rats subcutaneously (s.c.)implanted with YS or YS-R (each at 2×10
7 cells) were treated thereafter with i. p. administrations of CPM at 20,40, or 80 mg/kg. CPM was given in one bolus on the fifth postimplantation day, or divided into eight daily dosages from the same day on. Among the one bolus regimens,40 mg CPM was found to be most effective for survival of the YS-bearing rats; 80 mg CPM often caused death by intoxication. The same regimens enhanced tumoral growth in the YS-R bearing rats to yield an adverse effect. The divided dosage schedules exerted influences on the growths of the YS and the YS-R similar to those effected by the one bolus regimens, but the adverse effect on YS-R was not observed.
2) PH A response of spleen cells from tumor-bearing rats treated with CPM: After counting the total number of cells obtained from the spleen, each unit of 15×10
6 cells was cultivated with PHA, and examined for its 3HTdR uptake. The total response of each spleen was found by multiplying the reactivity of each culture by the total cell count.
Spleens of YS-bearing rats showed elevations in response during the early stage after tumor implantation, followed by a consistent descent in concomitance with tumor growth; such changes were not significant in rats bearing YS-R, which grew much more slowly than did the YS.
Normal rats administered with CPM 40 mg/kg showed suppression of their spleen responsiveness, being most remarkable on the 7th day after CPM administration, and recovering rapidly thereafter. This temporary depression was seen to be similar in all the CPM dosage schedules.
YS-bearing rats treated with CPM 40 mg/kg, both in one bolus and dividedly, showed, after a rapid and temporary depression in spleen responsiveness, recovery proportionate to tumor regression. On the contrary, YS-R bearing rats, in whom the tumor grew regardless of CPM administration, continued to lose spleen responsiveness without recovery.
These changes in spleen responsiveness were attributable not only to the increased or decreased number of spleen cells, but also to the changes in the mean reactivity of each spleen cell.
These obtained results show that, even after the administration of CPM, which is a potent immuno-depressant, the immunological activity of a tumor-bearing host can be restored in concomitance with tumoral regression, when the tumor is sensitive to the drug they may also make evident the rationality of immuno-chemotherapy, i. e. chem otherapy combined with immuno-stimulants.
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