Partial characterization of bone marrow hemopoiesis in mice after cisplatin administration

After cessation of cisplatin (cis-dichlorodiammineplatinum) chemotherapy, selective recovery of certain cell lineages occurs during bone marrow hemopoiesis. To further investigate the process of selective hemopoiesis, we combined the use of buoyant density gradient separation, morphology, and lymphocyte function assays to characterize changes in the hemopoiesis of immature and mature marrow cells after exposure to cisplatin. A single, cytotoxic dose of cisplatin was administered to B6D2F1 male mice, and marrow cell suspensions were taken from these mice 3 and 7 days later to characterize hemopoietic recovery. Morphology and buoyant density separation of marrow cells revealed that the most significant changes in cellular composition occurred at Day 3. At this time, there was an increase in immature white blood cells (WBCs) and immature polymorphoneutrophils (PMNs) with a concomitant reduction in immature red blood cells (RBCs). By Day 7, the normal proportion of immature RBCs, immature WBCs, and PMNs was restored; however, the buoyant distribution patterns for PMNs indicated that a greater proportion of immature PMNs was still present relative to marrow suspensions from normal mice. Fewer lymphocytes were also observed in marrows from the Day 7 group when compared with controls. Lymphocyte function tests indicated reduced mitogen responsiveness of lymphocytes from both Day 3 and Day 7; however, more immature lymphocytes were present after 7 days than were seen with either normal or Day 3 marrow suspensions. Overall, the results indicated that hemopoiesis proceeded through a specific hierarchy which began with the restoration of the erythrocyte line followed by the leukocyte cell lines. Lymphocyte recovery lagged behind the restoration of all the cell lineages examined.