THE EFFECT OF PROLONGED TREATMENT WITH HEMIN ON PLURIPOTENT HEMATOPOIETIC PROGENITORS OF NORMAL AND HEREDITARILY ANEMIC BELGRADE LABORATORY(B B) RATS/

The Belgrade laboratory (b/b) rat has an intracellular iron and haem d eficiency-induced anaemia, due to a mutation affecting intracellular i ron transport. Many disturbances in haemopoiesis of the b/b rat have b een described, including impaired proliferation and a decreased number of pluripotent and committed progenitor cells in bone marrow as well as expanded granulocytic and erythroid progenitor cell populations in the spleen. In this study, the effects treatment with haemin were eval uated on femoral and splenic pluripotent progenitors (spleen colony fo rming-units day 8, CFU-Sd8) in normal (+/+) and anaemic (b/b) rats. Th e treatment of b/b rats with haemin did not correct their severe anaem ia. However, the abrogation of the proliferative block and an increase d proliferative activity of the bone marrow CFU-Sd8 were found, demons trating that the proliferative block of the b/b rat bone marrow CFU-Sd 8 was induced by intracellular iron deficiency, rather than by severe hypoxia. Accordingly, the initially very low number of CFU-Sd8 per fem ur had increased, The results also revealed an enormously expanded pop ulation of splenic CFU-Sd8 in b/b rats, whereas after the haemin treat ment a significant decrease in the number of these cells was found. Th e treatment of +/+ rats with haemin resulted in a significant decrease in the number of femoral CFU-Sd8, but the cycling status of these cel ls was not affected. In the spleen, the initially low number of CFU-Sd 8 was modestly increased after the same treatment. These results imply that the effects of haemin treatment are different in a steady state than in a state of impaired medullar haemopoiesis. It is also evident that for both +/+ and b/b rats there exists an inverse number of CFU-S d8 in the bone marrow and spleen.