Residual damage of lymphohematopoietic repopulating cells after irradiation of mice at different stages of development.
OBJECTIVE
The purpose of this study was to evaluate the repopulating properties of bone marrow (BM) from mice irradiated during embryonic and adult stages of development.


METHODS
Four-day-old embryos, 17-day-old fetuses, and 12-week-old mice were irradiated with of 1 or 3 Gy of x-rays. At 3 and 9 months postirradiation, the effects generated within the different compartments of repopulating cells (RCs) were evaluated by determining, in a BM competition assay, the contribution of the irradiated precursors to the lymphohematopoiesis of recipients at different times posttransplantation (3, 9, and 15 months).


RESULTS
The irradiation of 4-day-old embryos with either 1 or 3 Gy did not produce residual repopulation or differentiation effects within the different RCs assayed. However, significant impairments in RC functionality were observed in mice irradiated on the 17th day postconception or at the 12th week of age. Whereas irradiation of these animals with 1 Gy did not impair the long-term functionality of the very primitive 15-month-old RCs, irradiation with 3 Gy generated sustained impairment in all tested types of hematopoietic progenitors and RCs. Moreover, repopulation data derived from the analysis of recipient BM and thymus strongly suggested that the observed effects were produced within the multipotent pool of lymphohematopoietic RCs.


CONCLUSIONS
Our data show the generation of long-term effects in the multipotent RCs of mice irradiated at fetal and adult stages of growth and reveals the normal functionality of the RCs from animals irradiated during the early stages of embryonic development.
Grande
T
T
Unidad de Biología Molecular y Celular, CIEMAT, Madrid, Spain.
Varas
F
F
Bueren
J A
JA
D000818:Animals; D001853:Bone Marrow / Q000254:growth & development* / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002455:Cell Division / Q000528:radiation effects; D003433:Crosses, Genetic; D004307:Dose-Response Relationship, Radiation; D004622:Embryo, Mammalian / Q000166:cytology / Q000528:radiation effects; D005260:Female; D005333:Fetus / Q000166:cytology / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000528:radiation effects*; D008214:Lymphocytes / Q000166:cytology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013950:Thymus Gland / Q000166:cytology / Q000528:radiation effects; D013997:Time Factors; D014916:Whole-Body Irradiation