Evidence for the reversibility of cellular DNA lesion induced by mammalian topoisomerase II poisons

Like many intercalative antitumor drugs, the nonintercalative antitumor drug epipodophyllotoxin VM-26 (teniposide) induces topoisomerase II-linked DNA breaks as revealed by cell lysis with a strong protein denaturant such as sodium dodecyl sulfate or alkali. We show that the majority of topoisomerase II-linked DNA breaks reflect the formation of reversible topoisomerase II-DNA cleavable complexes in drug-treated cells by demonstrating the reversibility of this unusual type of DNA damage at elevated temperatures (e.g. 65 degrees C).