Differential sensitivity of DBA/2 and C57BL/6 mice to cyclophosphamide

Abstract

Early and delayed toxicity of a single dose of 300 mg kg-1 cyclophosphamide (CP) was investigated in male DBA/2 and C57BL/6 mice. Early toxicity (up to 30 days after CP administration) resulted in 36.6% lethality in DBA/2 and no mortality in C57BL/6 mice. Delayed toxicity (after 30 days) occurred primarily in DBA/2 mice, resulting in a survival of 3% in DBA/2 and 93% in C57BL/6 mice on day 125 after CP administration. Early modifications brought about by CP in erythrocytes and leucocytes, and spleen and liver indexes (mg organ g-1 body wt.) were rather similar in DBA/2 and C57BL/6 strains. However, CP treatment caused a profound cell depletion in DBA/2 bone marrow owing, in part, to the fact that the number of cells in bone marrow of normal DBA/2 mice was much lower than that in normal C57BL/6 mice. Furthermore, the thymus index (mg organ g-1 body wt.) decreased sooner in DBA/2 than in C57BL/6 animals and no sign of recovery was evident in the former even after 10 days, whereas recovery in the latter started on day 5 after injection. Differential sensitivity of DBA/2 and C57BL/6 strains to CP could be due to differences in activation and/or inactivation of the drug, or to the increased effect of CP on DBA/2 bone marrow resulting in damage to pre-T cells that normally participate in thymus recovery.