Correlation between chromosome damage and apoptosis induced by fludarabine and idarubicin in normal human lymphocytes

Fludarabine (FLU, a fluorinated purine analog) and idarubicin (IDA, a DNA-topoisomerase II poison) are frequently used in cancer chemotherapy. The effects of these drugs on cultured normal human lymphocytes were studied to establish the possible involvement of chromosome damage in the apoptotic program. Chromosome aberrations (CA) were evaluated in first division metaphases and the apoptotic process was measured by morphological and electrophoretical techniques. The percentage of abnormal cells was increased from the doses of FLU 1.0 μg/ml and IDA 0.005 μg/ml (P<0.0001) with an important decrease in the mitotic index (MI) for the highest doses assayed. A significant dose-dependent induction of abnormal cells was observed for both drugs. An increase of apoptotic cells was found at 5.0 and 10.0 μg/ml of FLU (P<0.001) while IDA activated apoptosis at 0.05 μg/ml (P<0.01) and markedly from 0.1 μg/ml (P