Altered patterns of organ distribution of autologous and grafted blood cells in mice treated with hydroxyurea.

Migration and distribution of lymphocytes and red blood cells were profoundly altered in C57BL/6 mice treated with the anti-mitotic drug hydroxyurea (HU). HU treatment given twice daily for four consecutive days, markedly reduced the population of nucleated cells in the spleen and bone marrow; the numbers of nucleated cells in spleen and bone marrow were reduced to 20% and 10% of normal values, respectively. Paradoxically, in the bone marrow of HU-treated mice, the numbers of mature erythrocytes were increased 8-fold, while in the spleen erythrocyte values were decreased. To explore this altered pattern of red blood cell partition, radiolabeled cells were injected and their migration traced in normal and HU-treated recipients. Both erythrocyte and leukocyte populations were observed to migrate preferentially to the bone marrow of HU-treated animals. The altered pattern of blood cell partition in the bone marrow could be explained by the induction of abnormal permeability of the bone marrow-blood barrier by the antimitotic drug. This point may be of importance when considering clinical bone marrow transplantation. It stresses the need for antimitotic treatment before grafting individuals with hemopoietic precursors.