The effect of whole-body irradiation of nude mice on the tumor transplantability and control probability of a human soft tissue sarcoma xenograft.

This study has evaluated the impact of the suppression and recovery of the residual immunity in NCr/Sed nude (nu/nu) mice after whole-body irradiation using xenotransplantability and tumor control probability as the end points. For this investigation the xenograft was a human soft tissue sarcoma (HSTS26T). Two assays, the TD50 (the number of tumor cells required to induce a tumor in 50% of the recipients) and the TCD50 (the radiation dose required to control 50% of tumors) were used. For TD50 assays, tumor cells were injected subcutaneously (sc) into the legs of control and whole-body- irradiated nude mice at 1 day or 4, 8 or 12 weeks after irradiation. For TCD50 assays, tumors were transplanted sc into the legs of nude mice which had not been irradiated or which had been given whole-body irradiation at 1 day or 12 weeks prior to transplantation. The tumors were given single-dose irradiation when they reached 6 mm mean diameter under clamp-hypoxic conditions. The results show that the TD50's of mice receiving the injection 1 day and 4 and 8 weeks after whole-body irradiation were 3.6 to >100 times lower than that of unirradiated mice. Two groups which showed a statistically significant difference in TD50 's were those which received the injection 1 day and 8 weeks after whole-body irradiation (P < 0.01 and P < 0.05, respectively). No difference was found in TD50 values between mice that received injection 12 weeks after whole-body irradiation and those which were not irradiated. The TCD50 values of tumors in nonirradiated mice and in mice which had received whole-body irradiation 1 day and 12 weeks prior to to transplantation were 26.8, 44.1 and 33.9 Gy, respectively. Significantly lower TCD50 values were found in groups of nonirradiated mice or mice which received whole-body irradiation 12 weeks prior to transplantation in comparison with the group of mice that received whole-body irradiation on day 1 (both P < 0.05). No significant difference was found between the TCD50 values of the group of mice that received whole-body irradiation 12 weeks prior to transplantation and those for nonirradiated controls. Our conclusion is that the whole-body irradiation can enhance the transplantability of the HSTS26T tumor in nude mice significantly; this enhancing effect will decrease to the pre-irradiation level by 12 weeks after whole-body irradiation. Also, the suppression and recovery of residual immunity after whole-body irradiation can influence the TCD50 values of the same tumor xenografts in nude mice significantly. The changes in TD50 and TCD50 values correlate with the depletion and recovery of the total splenic lymphoid cell number, and especially in natural killer cell activity. We recommend that further immunosuppression in nude mice is necessary when using this model system for studies of human tumors.