Long-term haematological alterations in female B6C3F1 mice treated with busulphan

Female B6C3F(1) mice (12-14 weeks old) were dosed with busulphan (BU) by the intraperitoneal route at 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 (CAPS) at 4 mg/ml. Animals were killed at eight timepoints after the final BU dose, the last samples being taken at day 485 or 497 and a range of haematological parameters measured. During the experiment, no differences could be detected between mice receiving BU and CAPS and those receiving BU alone. Animals surviving to the end of the study displayed moderate leucopenia but no reduction in marrow cellularity nor was any effect on erythropoiesis apparent. Lymphocyte numbers were reduced in peripheral blood and bone marrow, and splenic cellularity was also reduced. Increased mortality was seen in animals which had received 40 mg BU/kg. In the first four months after BU dosing, animals killed due to ill health were pancytopenic with hypocellular marrows; deaths that occurred thereafter were due to lymphoma.