LONG-TERM EFFECTS OF BUSULFAN ON LYMPHOCYTE SUBPOPULATIONS IN FEMALE B6C3F(1) MICE

Female B6C3F(1) 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 fi nal dose, mice were given normal drinking water or drinking water cont aining chloramphenicol succinate (CAP.S) at 4 mg/ml. Animals were kill ed at eight timepoints after the final BU dose, the final samples bein g taken at day 485 or 497. A range of haematological parameters were d etermined and lymphocyte subsets analysed. The inclusion of CAP.S in t he drinking water did not affect the changes to haematological paramet ers 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 o ccasions except day 85. However, the lymphocyte count was increased to 107%-143% of control values in animals receiving 10 mg BU/kg on all o ccasions except day 85. The large unstained cell (LUC) count was reduc ed 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 B U 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 af fected by BU treatment. We have, therefore, demonstrated in the presen t study that administration of BU at high levels to the B6C3F(1) mouse induces a long-lasting and specific depletion of peripheral B lymphoc ytes; also, BU at low dose levels causes a mild but persistent lymphoc ytosis.