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Title: Hemopoietic stem-cell compartment of the SCID mouse: Double-exponential survival curve after [gamma] irradiation

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (United States)
 [1]; ; ; ;  [2];  [3];  [4]
  1. Yokohama City Univ. School of Medicine (Japan) Niigata Univ. (Japan)
  2. Yokohama City Univ. School of Medicine (Japan)
  3. Nagasaki Univ (Japan)
  4. Niigata Univ. (Japan)

It has been reported that SCID (severe combined immunodeficiency, scid/scid) mice are more radiosensitive than normal mice. In the present studies, graded doses of radiation were given to bone marrow cells from SCID mice, and double-exponential survival curves were observed for day-9 and day-12 colony-forming units in the spleen (CFU-S). Single-exponential curves were found for SCID CFU in in vitro assays for granulocyte/macrophage-CFUs and erythroid burst-forming units, as reported elsewhere. Since the size of this more resistant fraction seems to decrease with stem-cell maturation, the finding implies that this fraction is a primitive subpopulation of the stem-cell compartment. The mean lethal dose (D[sub 0]), however, of this less sensitive SCID CFU-S is much less than the D[sub 0] of regular CFU-S in normal littermates. Spleen colonies produced by SCID bone marrow were relatively small and abortive. The size of these colonies decreased nearly exponentially with increasing doses of radiation. These colonies produced by the sensitive fraction have disappeared, being killed by a relatively low dose of radiation. This observation might account for the high lymphomagenesis arising from primitive hemopoietic stem cells in SCID mice, because the smallness of the colonies suggests that there is unrepaired or misrepaired damage. Furthermore, this less sensitive fraction might be a source of the [open quotes]leaky[close quotes] change of T and B cells, possibly due to the induction of an equivocal repair system which appears in the later stages of life in the SCID mice. 34 refs., 5 figs., 3 tabs.

OSTI ID:
6280497
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 90:10; ISSN 0027-8424
Country of Publication:
United States
Language:
English