INVOLVEMENT OF THE BANE MARROW STROMA IN THE RESIDUAL HEMATOPOIETIC DAMAGE-INDUCED BY IRRADIATION OF ADULT AND YOUNG MICE

The analysis of femoral hematopoiesis of mice irradiated with 7 Gy x-r ays at the age of 1 and 12 weeks evidenced a differential hematopoieti c dysfunction in the long term. Significant hematopoietic damage was o bserved 1 year after irradiation of 12-week-old mice: a marked reducti on in the number of hematopoietic progenitors and a severe impairment in the self-renewal capacity of the colony-forming unit-spleen (CFU-S) population. In the case of the 1-week-old irradiated mice, normal val ues in the femoral hematopoietic progenitors were observed, although a significant impairment in the capacity for self-renewal of the CFU-S population was apparent. The role that the stromal cells played in the se hematopoietic failures was investigated by ectopic implantation of bone marrow from the irradiated animals into the renal capsule of noni rradiated mice. Bone marrow implants from both types of donor-irradiat ed mice developed ossicles that were incapable of sustaining normal va lues of host hematopoietic progenitors, thus indicating that radiation mediated long-term damage in the hematopoietic lodging capacity of th e stromal cells. However, analysis of the number of CFU-S generated pe r ossicle-derived spleen colony revealed that the irradiation of hemat opoietic stromas resulted in an improved self-renewal capacity of lodg ed unirradiated CFU-S precursors. Our data strongly suggest that the i mpairment in the long-term self-renewal capacity of the CFU-S populati on is not a result of the stromal damage. Rather, this stromal damage might actually generate a stimulatory response facilitating the preser vation of the low numbers of primitive precursors that survived the ir radiation.