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

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Gonzalez-Cid M, Fundia AF, Cuello MT, Larripa I

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

Toxicology. 2002 Feb 28;171(2-3):215-22.

PubMed ID

11836027 [ View in PubMed

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Abstract

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 microg/ml and IDA 0.005 microg/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 microg/ml of FLU (P<0.001) while IDA activated apoptosis at 0.05 microg/ml (P<0.01) and markedly from 0.1 microg/ml (P<0.001). These increments were dose dependent. Apoptotic cell morphology was associated with DNA fragmentation at the highest doses. The increased induction of abnormal cells and the decreased MI were in correlation with the apoptotic index for FLU and IDA, suggesting the role of CA in drug-induced cell death.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Idarubicin	DNA topoisomerase 2-alpha	Protein	Humans	Yes	Inhibitor	Details