A Role for Manganese Superoxide Dismutase in Radioprotection of Hematopoietic Stem Cells

Pretreatment with interleukin-I (IL-I) has been shown to protect mice from the myelotoxicity associated with irradiation via a mechanism potentially mediated through the induction of the antioxidant enzyme manganese superoxide dismutase (MnSOD). In this study, we have compared the abilityof IL-I to induce MnSOD mRNA in murine bone marrow cells and human cell lines with its ability to protect these cells against the damaging effects of ionizing radiation. Bone marrow cells obtained from mice 6 hours after a single injection of IL-I demonstrate a dose-dependent increase in the expression of MnSOD RNA. In this same study, IL-I was also shown to be radioprotective when given to mice 20 hours before lethal irradiation. Similarly, in vitro treatment with IL-I of bone marrow cells isolated from 5-fluorouracil-treated mice results in elevated levels of MnSOD RNA. Pretreatment with 11-1 also protected bone marrow long-term culture-initiating cells capable of reconstituting irradiated stromal cultures from an irradiation insult. Furthermore, IL-I -treated human bone marrow cells display both elevated MnSOD RNA and protein levels when