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).
Hsiang
Y H
YH
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Liu
L F
LF
D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D006367:HeLa Cells / Q000201:enzymology; D051379:Mice; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D013379:Substrate Specificity; D013713:Teniposide / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D013713:Teniposide; D011034:Podophyllotoxin