The relationship between sister chromatid exchange induction and leukemogenicity of different cytostatics

The genotoxicity of frequently used cytostatic agents was characterized by the enumeration of the sister chromatid exchanges (SCEs) induced by them in vivo in phytohemagglutinin-stimulated peripheral blood lymphocytes. Fifty-nine cancer patients undergoing and off chemotherapy are included in this study. The aim was to identify cytostatics according to their ability to alter the SCE frequency. Cytostatics with strong SCE-inducing ability (melphalan, cyclophosphamide, cyclophosphamide + vincristine + 5-fluorouracil, cyclophosphamide + vincristine + procarbazid + prednisolone) usually exhibited a longlasting SCE elevation. Cytosine arabinoside, hydroxyurea, vincristine, 5-fluorouracil, tamoxifen, and azathioprine did not induce SCEs. These data were compared with the leukemogenic potential of the same drugs in order to validate the relevance of SCE studies in man to signal carcinogenic hazards. It was found that over 80% of all secondary leukemias (collected from the world literature from 1930 to 1980) were preceded by the administration of cytotoxic compounds inducing long-lasting SCE elevation in lymphocytes. Only 3% of all secondary leukemias can be attributed to drugs not inducing SCEs in vivo in PHA-stimulated lymphocytes. This indicates that the lesions important for SCEs and secondary leukemias to emerge bear close biological similarities. Thus SCE studies can be used in selecting therapeutical protocols or new cytostatics with less carcinogenic potential to man.