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Effect of misonidazole on anti tumor activity of immunized rats that received total body irradiation



Effect of misonidazole on anti tumor activity of immunized rats that received total body irradiation



Nippon Acta Radiologica 41(12): 1209-1219



The hypoxic cell sensitizer misonidazole (MIS) was considered to sensitize the hypoxic tumor cells selectively. But some recent data suggests that MIS has a smaller sensitizing effect on normal tissue. In view of this, the experimental studies were performed to investigate the effect of MIS on antitumor activity of immunized rats that received total body irradiation (TBI). Male Wistar strain rats that received s.c. transplantations of [rat] Yoshida sarcoma cells (YS) were cured at high rates with tetramethylthiuram disulfide (TMTD), and at the same time, they acquired transplantation immunity that resists completely retransplantation of 107 YS. When these immunized rats received TBI, they lost their antitumor activity and died of the tumor after i.p. retransplantation of 107 YS. The mortality rates varied depending on the radiation doses of TBI. In immunized rats with TBI alone, the mortality rates were 0% at 450 rad, 12% at 550 rad and 44% at 650 rad. In immunized rats with MIS (0.5 g/kg i.p.) plus TBI, the mortality rates were 20% at 450 rad, 41% at 550 rad and 65% at 650 rad. The radiation dose for 50% abolishment of antitumor activity (50% death radiation dose) was 690 rad in immunized rats that received TBI alone and 580 rad in immunized rats that received TBI with MIS. MIS probably caused enhancement of radiation damage in antitumor activity of immunized rats. The enhancement ratio was 1.2. The neutralization test was made to investigate the effect of MIS on the antitumor activity of peritoneal exudate cells (PEC). Each PEC from immunized rats with 550 rad TBI alone and with MIS plus TBI were added to YS and incubated at 37.degree. C for 30 min. The mixtures were injected i.p. to untreated normal rats. The PEC from the immunized rats with MIS plus TBI did not inhibit the proliferation of YS sufficiently; the survival time of the untreated normal rats was shorter than those of immunized rats with TBI alone. MIS was, therefore, thought to also damage the antitumor [immune] activity of PEC.

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