Concurrent activation of granulocytes and osteoclasts in busulfan-suppressed bone marrow in response to transplantation of a mammary carcinoma in mice.

Transplantation of CE mammary adenocarcinoma (CE maca) into normal mice produces both neutrophilia and hypercalcemia due to osteoclastic bone resorption. In order to explore the physiology of osteoclast formation in vivo, the time course of neutrophilia and osteoclast development was examined in mice that had been pretreated with busulfan prior to the CE maca implantation. Busulfan-treated tumor-bearing mice (BUTUM), busulfan-treated control mice (BUCON), tumor-bearing mice with no busulfan (TUM), and normal controls (CON) were sacrificed on days 4, 7, 11, 14, and 17 after tumor implantation. Leukocyte counts, serum calcium levels, marrow cellularity, and marrow colony-forming units (CFU) were determined. Osteoclasts were quantified histologically by the osteoclast: endosteum ratio (OER). BUCON bone marrow was hypoplastic with CFU remaining significantly lower than that of controls over the course of the experiment. In contrast, BUTUM marrow CFU increased dramatically with the growth of the tumor. The most predominant increase was observed in neutrophilic CFU. Development of hypercalcemia closely paralleled neutrophilia in both TUM and BUTUM mice, although these changes were significantly delayed in the BUTUM group. The neutrophil count and serum calcium levels remained within normal control levels for BUCON mice. The OER correlated with serum calcium, and it closely paralleled the neutrophil count in TUM and BUTUM mice. These results clearly indicated the stimulation of bone marrow neutrophilic granulocyte progenitors and osteoclasts by the CE maca, indicating that the bone marrow is the primary target of this tumor. There may be a closely related mechanism in osteoclast and granulocyte stimulation by one or more CE maca factors.