DIFFERENTIAL SENSITIVITY OF DBA 2 AND C57BL/6 MICE TO CYCLOPHOSPHAMIDE/

Early and delayed toxicity of a single dose of 300 mg kg(-1) cyclophos phamide (CP) was investigated in male DBA/2 and C57BL/6 mice. Early to xicity (up to 30 days after CP administration) resulted in 36.6% letha lity in DBA/2 and no mortality in C57BL/6 mice. Delayed toxicity (afte r 30 days) occurred primarily in DBA/2 mice, resulting in a survival o f 3% in DBA/2 and 93% in C57BL/6 mice on day 125 after CP administrati on. Early modifications brought about by CP in erythrocytes and leucoc ytes, and spleen and liver indexes (mg organ g(-1) body wt.) were rath er 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 i ndex (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 afte r 10 days, whereas recovery in the latter started on day 5 after injec tion. Differential sensitivity of DBA/2 and C57BL/6 strains to CP coul d 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 da mage to pre-T cells that normally participate in thymus recovery.