Long-term effects of busulphan on lymphocyte subpopulations in female B6C3F1 mice

Abstract

Female B6C3F1 mice (12–14 weeks old) were dosed with busulphan (BU) by the intraperitoneal route at a range of dose levels between 10 and 40 mg/kg on four occasions at 14 day intervals. Six weeks after the final dose, mice were given normal drinking water or drinking water containing chloramphenicol succinate (CAP.S) at 4 mg/ml. Animals were killed at eight timepoints after the final BU dose, the final samples being taken at day 485 or 497. A range of haematological parameters were determined and lymphocyte subsets analysed. The inclusion of CAP.S in the drinking water did not affect the changes to haematological parameters or lymphocyte subsets induced by BU. Lymphocyte count was reduced to 51%–66% of control values in animals receiving 40 mg BU/kg on all occasions except day 85. However, the lymphocyte count was increased to 107%–143% of control values in animals receiving 10 mg BU/kg on all occasions except day 85. The large unstained cell (LUC) count was reduced to between 25%–47% of control values in animals receiving 40 mg BU/kg on all occasions, however, the LUC count was not increased at low BU dosage. At day 485/497, B lymphocyte counts were reduced to 48% (p<0.01), 64% (NS) and 55% (p<0.05) of control values in mice treated with 40, 33 and 25 mg BU/kg, respectively. T lymphocyte counts were not affected by BU treatment. We have, therefore, demonstrated in the present study that administration of BU at high levels to the B6C3F1 mouse induces a long-lasting and specific depletion of peripheral B lymphocytes; also, BU at low dose levels causes a mild but persistent lymphocytosis.