DNA fragmentation as a consequence of cell cycle traverse in doxorubicin- and idarubicin-treated human lymphoma cells.

Abstract:

:We have studied some of the factors involved in the cytotoxic actions of the anticancer anthracycline antibiotics doxorubicin (DOX) and idarubicin (IDA) towards human B-cell lymphoma cells in vitro. IDA was found to accumulate within cells to a greater degree than the related drug DOX for both short (1 h) and long-term (24 h) exposures. Both agents showed a similar capacity for trapping topoisomerase II in intact cells, but cross-linking activity was significantly lower than that induced by the specific poison VP16. IDA was four- to eight fold more potent for the induction of cytostasis and cell cycle arrest and for the instigation of DNA breakdown as a prelude to the full expression of apoptosis. Inhibition of DNA fragmentation at higher drug doses was linked closely with the inhibition of S-phase traverse. The findings suggest that DOX and IDA act in a similar fashion, the latter agent being more effective due to enhanced intracellular accumulation. We conclude that the presence of drug and topoisomerase II-associated DNA damage is not sufficient to induce DNA fragmentation; rather, unregulated commitment to S-phase traverse is an important factor in the activation of programmed cell death.

journal_name

Ann Hematol

journal_title

Annals of hematology

authors

Smith PJ,Rackstraw C,Cotter F

doi

10.1007/BF01757348

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

S7-11

eissn

0939-5555

issn

1432-0584

journal_volume

69 Suppl 1

pub_type

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