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A role for manganese superoxide dismutase in radioprotection of
hematopoietic stem cells by interleukin-1
J Eastgate, J Moreb, HS Nick, K Suzuki, N Taniguchi and JR Zucali
Department of Medicine, University of Florida, Gainesville 32610.
Pretreatment with interleukin-1 (IL-1) 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 ability
of IL-1 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-1 demonstrate a dose- dependent increase in the
expression of MnSOD RNA. In this same study, IL-1 was also shown to be
radioprotective when given to mice 20 hours before lethal irradiation.
Similarly, in vitro treatment with IL-1 of bone marrow cells isolated from
5-fluorouracil-treated mice results in elevated levels of MnSOD RNA.
Pretreatment with IL-1 also protected bone marrow long-term
culture-initiating cells capable of reconstituting irradiated stromal
cultures from an irradiation insult. Furthermore, IL-1-treated human bone
marrow cells display both elevated MnSOD RNA and protein levels when
compared with media controls. The human A375 melanoma, A549 adenocarcinoma,
and factor-dependent TF-1 leukemic cell lines demonstrate low basal MnSOD
RNA levels that increase following treatment with IL-1. For the A375 cells,
this correlates with increased MnSOD protein expression and radioprotection
by IL-1 using a colony assay. In contrast, the chronic myelogenous leukemic
cell line, K562, displays a high basal MnSOD RNA level, and this RNA
expression is not further increased by IL-1 treatment. In addition, these
cells are comparatively radioresistant and are not further protected by
IL-1 treatment. Finally, the Mo-7 cell line displays a low basal level of
MnSOD RNA that correlates with a high sensitivity to irradiation and IL-1
pretreatment has no effect on MnSOD RNA levels. Our results indicate that
increased radioprotection by IL-1 correlates with the induction of the
antioxidant enzyme MnSOD and this induction may be an important factor in
IL-1 radioprotection.
Volume 81,
Issue 3,
pp. 639-646,
02/01/1993
Copyright © 1993 by The American Society of Hematology
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