The immunomodulatory
alkaloid swainsonine (8alphabeta-indolizidine-1alpha,2alpha,8beta-triol) has potential for overcoming the bone marrow suppressive effects of
cancer chemotherapy and
radiotherapy. An earlier study showed that multiple doses of
swainsonine enhanced bone marrow cellularity in four different strains (C57BL/6; C3H-HEN; Balb/C and DBA-2 mice) of inbred mice which were not exposed to any chemotherapeutic agents or radiation. In vitro assessment of total colony formation capacity of bone marrow cells (BM CFUs) showed a 2- to 8-fold increase in
swainsonine-treated mice compared to control mice that were given
sham injections of physiological saline. In the current study, we have evaluated the functional competence of the bone marrow cells produced in response to
swainsonine treatment of normal healthy mice. In particular, colony forming units-granulocyte-macrophage (CFU-GM), erythroid-burst forming units (BFUe) and CFU-Mix (or CFU-granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM)) levels, were determined using in vitro assays. The time course of the changes in CFU-GM, BFUe and CFU-Mix (CFU-GEMM) were also followed. Our results demonstrate that
swainsonine bolsters the CFU capacity of BM cells without loss of function to levels which are several folds higher than in
sham-treated control mice.
Swainsonine treatment caused an increase in all lineages of marrow cells without loss of function. This effect was reproduced in all four strains of inbred mice in this investigation. Examination of the peripheral blood did not reveal increase in white blood cells or changes in the hematocrit levels. The long-term effects of
swainsonine treatment are not known at present. Nonetheless,
swainsonine-induced increase in CFU capacity of bone marrow cells and related cells along the different differentiation paths should find clinical application in
cancer treatment with chemotherapeutic agents and/or radiation.