Deoxyspergualin (DGS) is a new immunosuppressant which has shown inhibitory haemopoietic activity. We investigated the myeloprotective effect of DSG against the haemopoietic injury of mitomycin C (MMC) or cyclophosphamide (CYC) by measuring peripheral blood cell numbers in dogs. DSG given at 5 mg/kg on days 3, 2 and 1 before, or at 10 mg/kg on either days 2 and 1 before or on day 1 before and the day of injection of MMC at 0.25 mg/kg ameliorated both the thrombocytopenia and leucopenia caused by MMC. This ameliorative effect was more evident on platelet counts than on white blood cell counts. In addition, the leucopenia and thrombocytopenia induced by a single injection of CYC at 10 mg/kg was also ameliorated by prior DSG administration. These findings suggest that DSG may be useful in protecting against the haemopoietic damage induced by chemotherapeutic agents in the treatment of cancer.
We have examined the efficacy of deoxyspergualin (DSG) in protecting splenic colony‐forming cells (CFU‐S) from mitomycin C (MMC)‐induced damage. The main findings of the study are as follows. (1) When DSG was administered at doses of 1.5 and 3 mg/kg for 7 days before the MMC injection, the decrease of the femoral CFU‐S caused by MMC was diminished on the day after the MMC injection. The optimal dose was found to be 3 mg/kg. (2) In animals receiving 3 mg/kg DSG for at least 3 days preceding the MMC injection, the femoral CFU‐S was more than 200% of that in the MMC alone group one day after the MMC injection. (3) The number of femoral CFU‐S in the mice which received 3 mg/kg DSG for 3 days prior to MMC was significantly restored day by day and reached 70% of normal at 5 days after the MMC injection, while it was only 13% of normal in the MMC alone group. Moreover, the prior DSG administration significantly diminished the MMC toxicity to circulating platelets. (4) DSG administration (3 mg/kg) 3 days prior to MMC did not weaken the antitumor activity against colon 26 adenocarcinoma or P388 leukemia when compared with MMC alone. These findings have shown the ability of DSG specifically to protect the animals against bone marrow toxicity caused by MMC without interfering with the antitumor activity.
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