Specificity of melphalan-induced rearrangements and their transmission through cell divisions

The clastogenic effect of melphalan, an alkylating agent frequently used in chemotherapy, was investigated using chromosomes from human lymphocytes, two and three cell cycles after treatment in vitro. chromosome aberrations were much more frequent than chromatid type anomalies. Unbalanced rearrangements, i.e. deletions, dicentrics and complex rearrangements (in decreasing order of occurrence), were quite frequent and balanced rearrangements, such as reciprocal translocations and inversions, were quite rare. Deletions principally affected chromosomes 9, 5, 7 and 11. By comparison to the results obtained at first division after treatment, the relative frequencies of del(5) and del(20) increased with the number of cell divisions. Thus, these deletions were poorly eliminated by selection. This finding may be related to the fact that del(5) and del(20) are frequently observed in premalignant haemopathies.