EFFECT OF RECOMBINANT HUMAN MANGANESE SUPEROXIDE-DISMUTASE ON RADIOSENSITIVITY OF MURINE B-CELL LEUKEMIA (BCL1) CELLS

Recombinant human manganese superoxide dismutase (SOD) protects cells from oxidative damage and is known to ameliorate post-irradiation damage in mice exposed to whole body or localized chest irradiation. The concept behind the present experiments was to investigate whether it is possible to improve the outcome in leukemia following total body irradiation used as part of the conditioning prior to allogeneic bone marrow transplantation. We determined whether SOD protects leukemic cells from the effects of ionizing irradiation both in vitro and in vivo. Murine B cell leukemia (BCL1) cells, derived from tumor-bearing mice, were irradiated in vitro with or without SOD and injected into BALB/c mice. All mice receiving 10(4) unirradiated BCL1 cells developed leukemia and died within 19-39 days. In vitro exposure of BCL1 cells to 800 cGy or 1600 cGy abolished the potential to induce leukemia by inoculation with 10(4) or 10(6) BCL1 cells, respectively. Addition of SOD in vitro during irradiation increased the resistance of BCL1 cells to ionizing irradiation; all mice receiving 10(6) BCL1 cells previously exposed in vitro to 1200 cGy in the presence of SOD died of leukemia, whereas only 40% of mice receiving a similar inoculum of irradiated BCL1 cells died of leukemia. In contrast, when BCL1-bearing mice were irradiated with 600-800 cGy with or without intravenous injection of SOD (100 mg/kg) 30 minutes prior to irradiation, development of leukemia was unaffected. Residual leukemia cells following therapy were assessed by adoptive transfer of 10(5) spleen cells to secondary BALB/c recipients. Our data suggest that although SOD can protect leukemia exposed in vitro to ionizing radiation it may not provide radioprotective effects to tumor cells exposed to ionizing irradiation in vivo. These observations might be relevant for improving anti-leukemia effects by escalation of total body irradiation under the radioprotective effects of SOD in conjunction with bone marrow transplantation.